Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5030_5033del (p.Thr1677fs)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5030_5033del (p.Thr1677fs)
Variation ID: 37623 Accession: VCV000037623.59
- Type and length
-
Deletion, 4 bp
- Location
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Cytogenetic: 17q21.31 17: 43067649-43067652 (GRCh38) [ NCBI UCSC ] 17: 41219666-41219669 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Jun 17, 2024 Sep 8, 2016 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5030_5033del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Thr1677fs frameshift NM_001407571.1:c.4814_4817delTAAC NP_001394500.1:p.Thr1606Ilefs frameshift NM_001407581.1:c.5093_5096delTAAC NP_001394510.1:p.Thr1699Ilefs frameshift NM_001407582.1:c.5093_5096delTAAC NP_001394511.1:p.Thr1699Ilefs frameshift NM_001407583.1:c.5090_5093delTAAC NP_001394512.1:p.Thr1698Ilefs frameshift NM_001407585.1:c.5090_5093delTAAC NP_001394514.1:p.Thr1698Ilefs frameshift NM_001407587.1:c.5090_5093delTAAC NP_001394516.1:p.Thr1698Ilefs frameshift NM_001407590.1:c.5087_5090delTAAC NP_001394519.1:p.Thr1697Ilefs frameshift NM_001407591.1:c.5087_5090delTAAC NP_001394520.1:p.Thr1697Ilefs frameshift NM_001407593.1:c.5027_5030delTAAC NP_001394522.1:p.Thr1677Ilefs frameshift NM_001407594.1:c.5027_5030delTAAC NP_001394523.1:p.Thr1677Ilefs frameshift NM_001407596.1:c.5027_5030delTAAC NP_001394525.1:p.Thr1677Ilefs frameshift NM_001407597.1:c.5027_5030delTAAC NP_001394526.1:p.Thr1677Ilefs frameshift NM_001407598.1:c.5027_5030delTAAC NP_001394527.1:p.Thr1677Ilefs frameshift NM_001407602.1:c.5027_5030delTAAC NP_001394531.1:p.Thr1677Ilefs frameshift NM_001407603.1:c.5027_5030delTAAC NP_001394532.1:p.Thr1677Ilefs frameshift NM_001407605.1:c.5027_5030delTAAC NP_001394534.1:p.Thr1677Ilefs frameshift NM_001407610.1:c.5024_5027delTAAC NP_001394539.1:p.Thr1676Ilefs frameshift NM_001407611.1:c.5024_5027delTAAC NP_001394540.1:p.Thr1676Ilefs frameshift NM_001407612.1:c.5024_5027delTAAC NP_001394541.1:p.Thr1676Ilefs frameshift NM_001407613.1:c.5024_5027delTAAC NP_001394542.1:p.Thr1676Ilefs frameshift NM_001407614.1:c.5024_5027delTAAC NP_001394543.1:p.Thr1676Ilefs frameshift NM_001407615.1:c.5024_5027delTAAC NP_001394544.1:p.Thr1676Ilefs frameshift NM_001407616.1:c.5024_5027delTAAC NP_001394545.1:p.Thr1676Ilefs frameshift NM_001407617.1:c.5024_5027delTAAC NP_001394546.1:p.Thr1676Ilefs frameshift NM_001407618.1:c.5024_5027delTAAC NP_001394547.1:p.Thr1676Ilefs frameshift NM_001407619.1:c.5024_5027delTAAC NP_001394548.1:p.Thr1676Ilefs frameshift NM_001407620.1:c.5024_5027delTAAC NP_001394549.1:p.Thr1676Ilefs frameshift NM_001407621.1:c.5024_5027delTAAC NP_001394550.1:p.Thr1676Ilefs frameshift NM_001407622.1:c.5024_5027delTAAC NP_001394551.1:p.Thr1676Ilefs frameshift NM_001407623.1:c.5024_5027delTAAC NP_001394552.1:p.Thr1676Ilefs frameshift NM_001407624.1:c.5024_5027delTAAC NP_001394553.1:p.Thr1676Ilefs frameshift NM_001407625.1:c.5024_5027delTAAC NP_001394554.1:p.Thr1676Ilefs frameshift NM_001407626.1:c.5024_5027delTAAC NP_001394555.1:p.Thr1676Ilefs frameshift NM_001407627.1:c.5021_5024delTAAC NP_001394556.1:p.Thr1675Ilefs frameshift NM_001407628.1:c.5021_5024delTAAC NP_001394557.1:p.Thr1675Ilefs frameshift NM_001407629.1:c.5021_5024delTAAC NP_001394558.1:p.Thr1675Ilefs frameshift NM_001407630.1:c.5021_5024delTAAC NP_001394559.1:p.Thr1675Ilefs frameshift NM_001407631.1:c.5021_5024delTAAC NP_001394560.1:p.Thr1675Ilefs frameshift NM_001407632.1:c.5021_5024delTAAC NP_001394561.1:p.Thr1675Ilefs frameshift NM_001407633.1:c.5021_5024delTAAC NP_001394562.1:p.Thr1675Ilefs frameshift NM_001407634.1:c.5021_5024delTAAC NP_001394563.1:p.Thr1675Ilefs frameshift NM_001407635.1:c.5021_5024delTAAC NP_001394564.1:p.Thr1675Ilefs frameshift NM_001407636.1:c.5021_5024delTAAC NP_001394565.1:p.Thr1675Ilefs frameshift NM_001407637.1:c.5021_5024delTAAC NP_001394566.1:p.Thr1675Ilefs frameshift NM_001407638.1:c.5021_5024delTAAC NP_001394567.1:p.Thr1675Ilefs frameshift NM_001407639.1:c.5021_5024delTAAC NP_001394568.1:p.Thr1675Ilefs frameshift NM_001407640.1:c.5021_5024delTAAC NP_001394569.1:p.Thr1675Ilefs frameshift NM_001407641.1:c.5021_5024delTAAC NP_001394570.1:p.Thr1675Ilefs frameshift NM_001407642.1:c.5021_5024delTAAC NP_001394571.1:p.Thr1675Ilefs frameshift NM_001407644.1:c.5018_5021delTAAC NP_001394573.1:p.Thr1674Ilefs frameshift NM_001407645.1:c.5018_5021delTAAC NP_001394574.1:p.Thr1674Ilefs frameshift NM_001407646.1:c.5015_5018delTAAC NP_001394575.1:p.Thr1673Ilefs frameshift NM_001407647.1:c.5012_5015delTAAC NP_001394576.1:p.Thr1672Ilefs frameshift NM_001407648.1:c.4970_4973delTAAC NP_001394577.1:p.Thr1658Ilefs frameshift NM_001407649.1:c.4967_4970delTAAC NP_001394578.1:p.Thr1657Ilefs frameshift NM_001407652.1:c.5027_5030delTAAC NP_001394581.1:p.Thr1677Ilefs frameshift NM_001407653.1:c.4949_4952delTAAC NP_001394582.1:p.Thr1651Ilefs frameshift NM_001407654.1:c.4949_4952delTAAC NP_001394583.1:p.Thr1651Ilefs frameshift NM_001407655.1:c.4949_4952delTAAC NP_001394584.1:p.Thr1651Ilefs frameshift NM_001407656.1:c.4946_4949delTAAC NP_001394585.1:p.Thr1650Ilefs frameshift NM_001407657.1:c.4946_4949delTAAC NP_001394586.1:p.Thr1650Ilefs frameshift NM_001407658.1:c.4946_4949delTAAC NP_001394587.1:p.Thr1650Ilefs frameshift NM_001407659.1:c.4943_4946delTAAC NP_001394588.1:p.Thr1649Ilefs frameshift NM_001407660.1:c.4943_4946delTAAC NP_001394589.1:p.Thr1649Ilefs frameshift NM_001407661.1:c.4943_4946delTAAC NP_001394590.1:p.Thr1649Ilefs frameshift NM_001407662.1:c.4943_4946delTAAC NP_001394591.1:p.Thr1649Ilefs frameshift NM_001407663.1:c.4943_4946delTAAC NP_001394592.1:p.Thr1649Ilefs frameshift NM_001407664.1:c.4904_4907delTAAC NP_001394593.1:p.Thr1636Ilefs frameshift NM_001407665.1:c.4904_4907delTAAC NP_001394594.1:p.Thr1636Ilefs frameshift NM_001407666.1:c.4904_4907delTAAC NP_001394595.1:p.Thr1636Ilefs frameshift NM_001407667.1:c.4904_4907delTAAC NP_001394596.1:p.Thr1636Ilefs frameshift NM_001407668.1:c.4904_4907delTAAC NP_001394597.1:p.Thr1636Ilefs frameshift NM_001407669.1:c.4904_4907delTAAC NP_001394598.1:p.Thr1636Ilefs frameshift NM_001407670.1:c.4901_4904delTAAC NP_001394599.1:p.Thr1635Ilefs frameshift NM_001407671.1:c.4901_4904delTAAC NP_001394600.1:p.Thr1635Ilefs frameshift NM_001407672.1:c.4901_4904delTAAC NP_001394601.1:p.Thr1635Ilefs frameshift NM_001407673.1:c.4901_4904delTAAC NP_001394602.1:p.Thr1635Ilefs frameshift NM_001407674.1:c.4901_4904delTAAC NP_001394603.1:p.Thr1635Ilefs frameshift NM_001407675.1:c.4901_4904delTAAC NP_001394604.1:p.Thr1635Ilefs frameshift NM_001407676.1:c.4901_4904delTAAC NP_001394605.1:p.Thr1635Ilefs frameshift NM_001407677.1:c.4901_4904delTAAC NP_001394606.1:p.Thr1635Ilefs frameshift NM_001407678.1:c.4901_4904delTAAC NP_001394607.1:p.Thr1635Ilefs frameshift NM_001407679.1:c.4901_4904delTAAC NP_001394608.1:p.Thr1635Ilefs frameshift NM_001407680.1:c.4901_4904delTAAC NP_001394609.1:p.Thr1635Ilefs frameshift NM_001407681.1:c.4898_4901delTAAC NP_001394610.1:p.Thr1634Ilefs frameshift NM_001407682.1:c.4898_4901delTAAC NP_001394611.1:p.Thr1634Ilefs frameshift NM_001407683.1:c.4898_4901delTAAC NP_001394612.1:p.Thr1634Ilefs frameshift NM_001407684.1:c.5027_5030delTAAC NP_001394613.1:p.Thr1677Ilefs frameshift NM_001407685.1:c.4898_4901delTAAC NP_001394614.1:p.Thr1634Ilefs frameshift NM_001407686.1:c.4898_4901delTAAC NP_001394615.1:p.Thr1634Ilefs frameshift NM_001407687.1:c.4898_4901delTAAC NP_001394616.1:p.Thr1634Ilefs frameshift NM_001407688.1:c.4898_4901delTAAC NP_001394617.1:p.Thr1634Ilefs frameshift NM_001407689.1:c.4898_4901delTAAC NP_001394618.1:p.Thr1634Ilefs frameshift NM_001407690.1:c.4895_4898delTAAC NP_001394619.1:p.Thr1633Ilefs frameshift NM_001407691.1:c.4895_4898delTAAC NP_001394620.1:p.Thr1633Ilefs frameshift NM_001407692.1:c.4886_4889delTAAC NP_001394621.1:p.Thr1630Ilefs frameshift NM_001407694.1:c.4886_4889delTAAC NP_001394623.1:p.Thr1630Ilefs frameshift NM_001407695.1:c.4886_4889delTAAC NP_001394624.1:p.Thr1630Ilefs frameshift NM_001407696.1:c.4886_4889delTAAC NP_001394625.1:p.Thr1630Ilefs frameshift NM_001407697.1:c.4886_4889delTAAC NP_001394626.1:p.Thr1630Ilefs frameshift NM_001407698.1:c.4886_4889delTAAC NP_001394627.1:p.Thr1630Ilefs frameshift NM_001407724.1:c.4886_4889delTAAC NP_001394653.1:p.Thr1630Ilefs frameshift NM_001407725.1:c.4886_4889delTAAC NP_001394654.1:p.Thr1630Ilefs frameshift NM_001407726.1:c.4886_4889delTAAC NP_001394655.1:p.Thr1630Ilefs frameshift NM_001407727.1:c.4886_4889delTAAC NP_001394656.1:p.Thr1630Ilefs frameshift NM_001407728.1:c.4886_4889delTAAC NP_001394657.1:p.Thr1630Ilefs frameshift NM_001407729.1:c.4886_4889delTAAC NP_001394658.1:p.Thr1630Ilefs frameshift NM_001407730.1:c.4886_4889delTAAC NP_001394659.1:p.Thr1630Ilefs frameshift NM_001407731.1:c.4886_4889delTAAC NP_001394660.1:p.Thr1630Ilefs frameshift NM_001407732.1:c.4883_4886delTAAC NP_001394661.1:p.Thr1629Ilefs frameshift NM_001407733.1:c.4883_4886delTAAC NP_001394662.1:p.Thr1629Ilefs frameshift NM_001407734.1:c.4883_4886delTAAC NP_001394663.1:p.Thr1629Ilefs frameshift NM_001407735.1:c.4883_4886delTAAC NP_001394664.1:p.Thr1629Ilefs frameshift NM_001407736.1:c.4883_4886delTAAC NP_001394665.1:p.Thr1629Ilefs frameshift NM_001407737.1:c.4883_4886delTAAC NP_001394666.1:p.Thr1629Ilefs frameshift NM_001407738.1:c.4883_4886delTAAC NP_001394667.1:p.Thr1629Ilefs frameshift NM_001407739.1:c.4883_4886delTAAC NP_001394668.1:p.Thr1629Ilefs frameshift NM_001407740.1:c.4883_4886delTAAC NP_001394669.1:p.Thr1629Ilefs frameshift NM_001407741.1:c.4883_4886delTAAC NP_001394670.1:p.Thr1629Ilefs frameshift NM_001407742.1:c.4883_4886delTAAC NP_001394671.1:p.Thr1629Ilefs frameshift NM_001407743.1:c.4883_4886delTAAC NP_001394672.1:p.Thr1629Ilefs frameshift NM_001407744.1:c.4883_4886delTAAC NP_001394673.1:p.Thr1629Ilefs frameshift NM_001407745.1:c.4883_4886delTAAC NP_001394674.1:p.Thr1629Ilefs frameshift NM_001407746.1:c.4883_4886delTAAC NP_001394675.1:p.Thr1629Ilefs frameshift NM_001407747.1:c.4883_4886delTAAC NP_001394676.1:p.Thr1629Ilefs frameshift NM_001407748.1:c.4883_4886delTAAC NP_001394677.1:p.Thr1629Ilefs frameshift NM_001407749.1:c.4883_4886delTAAC NP_001394678.1:p.Thr1629Ilefs frameshift NM_001407750.1:c.4883_4886delTAAC NP_001394679.1:p.Thr1629Ilefs frameshift NM_001407751.1:c.4883_4886delTAAC NP_001394680.1:p.Thr1629Ilefs frameshift NM_001407752.1:c.4883_4886delTAAC NP_001394681.1:p.Thr1629Ilefs frameshift NM_001407838.1:c.4880_4883delTAAC NP_001394767.1:p.Thr1628Ilefs frameshift NM_001407839.1:c.4880_4883delTAAC NP_001394768.1:p.Thr1628Ilefs frameshift NM_001407841.1:c.4880_4883delTAAC NP_001394770.1:p.Thr1628Ilefs frameshift NM_001407842.1:c.4880_4883delTAAC NP_001394771.1:p.Thr1628Ilefs frameshift NM_001407843.1:c.4880_4883delTAAC NP_001394772.1:p.Thr1628Ilefs frameshift NM_001407844.1:c.4880_4883delTAAC NP_001394773.1:p.Thr1628Ilefs frameshift NM_001407845.1:c.4880_4883delTAAC NP_001394774.1:p.Thr1628Ilefs frameshift NM_001407846.1:c.4880_4883delTAAC NP_001394775.1:p.Thr1628Ilefs frameshift NM_001407847.1:c.4880_4883delTAAC NP_001394776.1:p.Thr1628Ilefs frameshift NM_001407848.1:c.4880_4883delTAAC NP_001394777.1:p.Thr1628Ilefs frameshift NM_001407849.1:c.4880_4883delTAAC NP_001394778.1:p.Thr1628Ilefs frameshift NM_001407850.1:c.4880_4883delTAAC NP_001394779.1:p.Thr1628Ilefs frameshift NM_001407851.1:c.4880_4883delTAAC NP_001394780.1:p.Thr1628Ilefs frameshift NM_001407852.1:c.4880_4883delTAAC NP_001394781.1:p.Thr1628Ilefs frameshift NM_001407853.1:c.4880_4883delTAAC NP_001394782.1:p.Thr1628Ilefs frameshift NM_001407854.1:c.5027_5030delTAAC NP_001394783.1:p.Thr1677Ilefs frameshift NM_001407858.1:c.5024_5027delTAAC NP_001394787.1:p.Thr1676Ilefs frameshift NM_001407859.1:c.5024_5027delTAAC NP_001394788.1:p.Thr1676Ilefs frameshift NM_001407860.1:c.5024_5027delTAAC NP_001394789.1:p.Thr1676Ilefs frameshift NM_001407861.1:c.5021_5024delTAAC NP_001394790.1:p.Thr1675Ilefs frameshift NM_001407862.1:c.4826_4829delTAAC NP_001394791.1:p.Thr1610Ilefs frameshift NM_001407863.1:c.4901_4904delTAAC NP_001394792.1:p.Thr1635Ilefs frameshift NM_001407874.1:c.4820_4823delTAAC NP_001394803.1:p.Thr1608Ilefs frameshift NM_001407875.1:c.4820_4823delTAAC NP_001394804.1:p.Thr1608Ilefs frameshift NM_001407879.1:c.4817_4820delTAAC NP_001394808.1:p.Thr1607Ilefs frameshift NM_001407881.1:c.4817_4820delTAAC NP_001394810.1:p.Thr1607Ilefs frameshift NM_001407882.1:c.4817_4820delTAAC NP_001394811.1:p.Thr1607Ilefs frameshift NM_001407884.1:c.4817_4820delTAAC NP_001394813.1:p.Thr1607Ilefs frameshift NM_001407885.1:c.4817_4820delTAAC NP_001394814.1:p.Thr1607Ilefs frameshift NM_001407886.1:c.4817_4820delTAAC NP_001394815.1:p.Thr1607Ilefs frameshift NM_001407887.1:c.4817_4820delTAAC NP_001394816.1:p.Thr1607Ilefs frameshift NM_001407889.1:c.4817_4820delTAAC NP_001394818.1:p.Thr1607Ilefs frameshift NM_001407894.1:c.4814_4817delTAAC NP_001394823.1:p.Thr1606Ilefs frameshift NM_001407895.1:c.4814_4817delTAAC NP_001394824.1:p.Thr1606Ilefs frameshift NM_001407896.1:c.4814_4817delTAAC NP_001394825.1:p.Thr1606Ilefs frameshift NM_001407897.1:c.4814_4817delTAAC NP_001394826.1:p.Thr1606Ilefs frameshift NM_001407898.1:c.4814_4817delTAAC NP_001394827.1:p.Thr1606Ilefs frameshift NM_001407899.1:c.4814_4817delTAAC NP_001394828.1:p.Thr1606Ilefs frameshift NM_001407900.1:c.4814_4817delTAAC NP_001394829.1:p.Thr1606Ilefs frameshift NM_001407902.1:c.4814_4817delTAAC NP_001394831.1:p.Thr1606Ilefs frameshift NM_001407904.1:c.4814_4817delTAAC NP_001394833.1:p.Thr1606Ilefs frameshift NM_001407906.1:c.4814_4817delTAAC NP_001394835.1:p.Thr1606Ilefs frameshift NM_001407907.1:c.4814_4817delTAAC NP_001394836.1:p.Thr1606Ilefs frameshift NM_001407908.1:c.4814_4817delTAAC NP_001394837.1:p.Thr1606Ilefs frameshift NM_001407909.1:c.4814_4817delTAAC NP_001394838.1:p.Thr1606Ilefs frameshift NM_001407910.1:c.4814_4817delTAAC NP_001394839.1:p.Thr1606Ilefs frameshift NM_001407915.1:c.4811_4814delTAAC NP_001394844.1:p.Thr1605Ilefs frameshift NM_001407916.1:c.4811_4814delTAAC NP_001394845.1:p.Thr1605Ilefs frameshift NM_001407917.1:c.4811_4814delTAAC NP_001394846.1:p.Thr1605Ilefs frameshift NM_001407918.1:c.4811_4814delTAAC NP_001394847.1:p.Thr1605Ilefs frameshift NM_001407919.1:c.4904_4907delTAAC NP_001394848.1:p.Thr1636Ilefs frameshift NM_001407920.1:c.4763_4766delTAAC NP_001394849.1:p.Thr1589Ilefs frameshift NM_001407921.1:c.4763_4766delTAAC NP_001394850.1:p.Thr1589Ilefs frameshift NM_001407922.1:c.4763_4766delTAAC NP_001394851.1:p.Thr1589Ilefs frameshift NM_001407923.1:c.4763_4766delTAAC NP_001394852.1:p.Thr1589Ilefs frameshift NM_001407924.1:c.4763_4766delTAAC NP_001394853.1:p.Thr1589Ilefs frameshift NM_001407925.1:c.4763_4766delTAAC NP_001394854.1:p.Thr1589Ilefs frameshift NM_001407926.1:c.4763_4766delTAAC NP_001394855.1:p.Thr1589Ilefs frameshift NM_001407927.1:c.4760_4763delTAAC NP_001394856.1:p.Thr1588Ilefs frameshift NM_001407928.1:c.4760_4763delTAAC NP_001394857.1:p.Thr1588Ilefs frameshift NM_001407929.1:c.4760_4763delTAAC NP_001394858.1:p.Thr1588Ilefs frameshift NM_001407930.1:c.4760_4763delTAAC NP_001394859.1:p.Thr1588Ilefs frameshift NM_001407931.1:c.4760_4763delTAAC NP_001394860.1:p.Thr1588Ilefs frameshift NM_001407932.1:c.4760_4763delTAAC NP_001394861.1:p.Thr1588Ilefs frameshift NM_001407933.1:c.4760_4763delTAAC NP_001394862.1:p.Thr1588Ilefs frameshift NM_001407934.1:c.4757_4760delTAAC NP_001394863.1:p.Thr1587Ilefs frameshift NM_001407935.1:c.4757_4760delTAAC NP_001394864.1:p.Thr1587Ilefs frameshift NM_001407936.1:c.4757_4760delTAAC NP_001394865.1:p.Thr1587Ilefs frameshift NM_001407937.1:c.4904_4907delTAAC NP_001394866.1:p.Thr1636Ilefs frameshift NM_001407938.1:c.4904_4907delTAAC NP_001394867.1:p.Thr1636Ilefs frameshift NM_001407939.1:c.4901_4904delTAAC NP_001394868.1:p.Thr1635Ilefs frameshift NM_001407940.1:c.4901_4904delTAAC NP_001394869.1:p.Thr1635Ilefs frameshift NM_001407941.1:c.4898_4901delTAAC NP_001394870.1:p.Thr1634Ilefs frameshift NM_001407942.1:c.4886_4889delTAAC NP_001394871.1:p.Thr1630Ilefs frameshift NM_001407943.1:c.4883_4886delTAAC NP_001394872.1:p.Thr1629Ilefs frameshift NM_001407944.1:c.4883_4886delTAAC NP_001394873.1:p.Thr1629Ilefs frameshift NM_001407945.1:c.4883_4886delTAAC NP_001394874.1:p.Thr1629Ilefs frameshift NM_001407946.1:c.4694_4697delTAAC NP_001394875.1:p.Thr1566Ilefs frameshift NM_001407947.1:c.4694_4697delTAAC NP_001394876.1:p.Thr1566Ilefs frameshift NM_001407948.1:c.4694_4697delTAAC NP_001394877.1:p.Thr1566Ilefs frameshift NM_001407949.1:c.4694_4697delTAAC NP_001394878.1:p.Thr1566Ilefs frameshift NM_001407950.1:c.4691_4694delTAAC NP_001394879.1:p.Thr1565Ilefs frameshift NM_001407951.1:c.4691_4694delTAAC NP_001394880.1:p.Thr1565Ilefs frameshift NM_001407952.1:c.4691_4694delTAAC NP_001394881.1:p.Thr1565Ilefs frameshift NM_001407953.1:c.4691_4694delTAAC NP_001394882.1:p.Thr1565Ilefs frameshift NM_001407954.1:c.4691_4694delTAAC NP_001394883.1:p.Thr1565Ilefs frameshift NM_001407955.1:c.4691_4694delTAAC NP_001394884.1:p.Thr1565Ilefs frameshift NM_001407956.1:c.4688_4691delTAAC NP_001394885.1:p.Thr1564Ilefs frameshift NM_001407957.1:c.4688_4691delTAAC NP_001394886.1:p.Thr1564Ilefs frameshift NM_001407958.1:c.4688_4691delTAAC NP_001394887.1:p.Thr1564Ilefs frameshift NM_001407959.1:c.4646_4649delTAAC NP_001394888.1:p.Thr1550Ilefs frameshift NM_001407960.1:c.4643_4646delTAAC NP_001394889.1:p.Thr1549Ilefs frameshift NM_001407962.1:c.4643_4646delTAAC NP_001394891.1:p.Thr1549Ilefs frameshift NM_001407963.1:c.4640_4643delTAAC NP_001394892.1:p.Thr1548Ilefs frameshift NM_001407964.1:c.4565_4568delTAAC NP_001394893.1:p.Thr1523Ilefs frameshift NM_001407965.1:c.4520_4523delTAAC NP_001394894.1:p.Thr1508Ilefs frameshift NM_001407966.1:c.4139_4142delTAAC NP_001394895.1:p.Thr1381Ilefs frameshift NM_001407967.1:c.4136_4139delTAAC NP_001394896.1:p.Thr1380Ilefs frameshift NM_001407968.1:c.2423_2426delTAAC NP_001394897.1:p.Thr809Ilefs frameshift NM_001407969.1:c.2420_2423delTAAC NP_001394898.1:p.Thr808Ilefs frameshift NM_001407970.1:c.1784_1787delTAAC NP_001394899.1:p.Thr596Ilefs frameshift NM_001407971.1:c.1784_1787delTAAC NP_001394900.1:p.Thr596Ilefs frameshift NM_001407972.1:c.1781_1784delTAAC NP_001394901.1:p.Thr595Ilefs frameshift NM_001407973.1:c.1718_1721delTAAC NP_001394902.1:p.Thr574Ilefs frameshift NM_001407974.1:c.1718_1721delTAAC NP_001394903.1:p.Thr574Ilefs frameshift NM_001407975.1:c.1718_1721delTAAC NP_001394904.1:p.Thr574Ilefs frameshift NM_001407976.1:c.1718_1721delTAAC NP_001394905.1:p.Thr574Ilefs frameshift NM_001407977.1:c.1718_1721delTAAC NP_001394906.1:p.Thr574Ilefs frameshift NM_001407978.1:c.1718_1721delTAAC NP_001394907.1:p.Thr574Ilefs frameshift NM_001407979.1:c.1715_1718delTAAC NP_001394908.1:p.Thr573Ilefs frameshift NM_001407980.1:c.1715_1718delTAAC NP_001394909.1:p.Thr573Ilefs frameshift NM_001407981.1:c.1715_1718delTAAC NP_001394910.1:p.Thr573Ilefs frameshift NM_001407982.1:c.1715_1718delTAAC NP_001394911.1:p.Thr573Ilefs frameshift NM_001407983.1:c.1715_1718delTAAC NP_001394912.1:p.Thr573Ilefs frameshift NM_001407984.1:c.1715_1718delTAAC NP_001394913.1:p.Thr573Ilefs frameshift NM_001407985.1:c.1715_1718delTAAC NP_001394914.1:p.Thr573Ilefs frameshift NM_001407986.1:c.1715_1718delTAAC NP_001394915.1:p.Thr573Ilefs frameshift NM_001407990.1:c.1715_1718delTAAC NP_001394919.1:p.Thr573Ilefs frameshift NM_001407991.1:c.1715_1718delTAAC NP_001394920.1:p.Thr573Ilefs frameshift NM_001407992.1:c.1715_1718delTAAC NP_001394921.1:p.Thr573Ilefs frameshift NM_001407993.1:c.1715_1718delTAAC NP_001394922.1:p.Thr573Ilefs frameshift NM_001408392.1:c.1712_1715delTAAC NP_001395321.1:p.Thr572Ilefs frameshift NM_001408396.1:c.1712_1715delTAAC NP_001395325.1:p.Thr572Ilefs frameshift NM_001408397.1:c.1712_1715delTAAC NP_001395326.1:p.Thr572Ilefs frameshift NM_001408398.1:c.1712_1715delTAAC NP_001395327.1:p.Thr572Ilefs frameshift NM_001408399.1:c.1712_1715delTAAC NP_001395328.1:p.Thr572Ilefs frameshift NM_001408400.1:c.1712_1715delTAAC NP_001395329.1:p.Thr572Ilefs frameshift NM_001408401.1:c.1712_1715delTAAC NP_001395330.1:p.Thr572Ilefs frameshift NM_001408402.1:c.1712_1715delTAAC NP_001395331.1:p.Thr572Ilefs frameshift NM_001408403.1:c.1712_1715delTAAC NP_001395332.1:p.Thr572Ilefs frameshift NM_001408404.1:c.1712_1715delTAAC NP_001395333.1:p.Thr572Ilefs frameshift NM_001408406.1:c.1709_1712delTAAC NP_001395335.1:p.Thr571Ilefs frameshift NM_001408407.1:c.1709_1712delTAAC NP_001395336.1:p.Thr571Ilefs frameshift NM_001408408.1:c.1709_1712delTAAC NP_001395337.1:p.Thr571Ilefs frameshift NM_001408409.1:c.1706_1709delTAAC NP_001395338.1:p.Thr570Ilefs frameshift NM_001408410.1:c.1643_1646delTAAC NP_001395339.1:p.Thr549Ilefs frameshift NM_001408411.1:c.1640_1643delTAAC NP_001395340.1:p.Thr548Ilefs frameshift NM_001408412.1:c.1637_1640delTAAC NP_001395341.1:p.Thr547Ilefs frameshift NM_001408413.1:c.1637_1640delTAAC NP_001395342.1:p.Thr547Ilefs frameshift NM_001408414.1:c.1637_1640delTAAC NP_001395343.1:p.Thr547Ilefs frameshift NM_001408415.1:c.1637_1640delTAAC NP_001395344.1:p.Thr547Ilefs frameshift NM_001408416.1:c.1637_1640delTAAC NP_001395345.1:p.Thr547Ilefs frameshift NM_001408418.1:c.1601_1604delTAAC NP_001395347.1:p.Thr535Ilefs frameshift NM_001408419.1:c.1601_1604delTAAC NP_001395348.1:p.Thr535Ilefs frameshift NM_001408420.1:c.1601_1604delTAAC NP_001395349.1:p.Thr535Ilefs frameshift NM_001408421.1:c.1598_1601delTAAC NP_001395350.1:p.Thr534Ilefs frameshift NM_001408422.1:c.1598_1601delTAAC NP_001395351.1:p.Thr534Ilefs frameshift NM_001408423.1:c.1598_1601delTAAC NP_001395352.1:p.Thr534Ilefs frameshift NM_001408424.1:c.1598_1601delTAAC NP_001395353.1:p.Thr534Ilefs frameshift NM_001408425.1:c.1595_1598delTAAC NP_001395354.1:p.Thr533Ilefs frameshift NM_001408426.1:c.1595_1598delTAAC NP_001395355.1:p.Thr533Ilefs frameshift NM_001408427.1:c.1595_1598delTAAC NP_001395356.1:p.Thr533Ilefs frameshift NM_001408428.1:c.1595_1598delTAAC NP_001395357.1:p.Thr533Ilefs frameshift NM_001408429.1:c.1595_1598delTAAC NP_001395358.1:p.Thr533Ilefs frameshift NM_001408430.1:c.1595_1598delTAAC NP_001395359.1:p.Thr533Ilefs frameshift NM_001408431.1:c.1595_1598delTAAC NP_001395360.1:p.Thr533Ilefs frameshift NM_001408432.1:c.1592_1595delTAAC NP_001395361.1:p.Thr532Ilefs frameshift NM_001408433.1:c.1592_1595delTAAC NP_001395362.1:p.Thr532Ilefs frameshift NM_001408434.1:c.1592_1595delTAAC NP_001395363.1:p.Thr532Ilefs frameshift NM_001408435.1:c.1592_1595delTAAC NP_001395364.1:p.Thr532Ilefs frameshift NM_001408436.1:c.1592_1595delTAAC NP_001395365.1:p.Thr532Ilefs frameshift NM_001408437.1:c.1592_1595delTAAC NP_001395366.1:p.Thr532Ilefs frameshift NM_001408438.1:c.1592_1595delTAAC NP_001395367.1:p.Thr532Ilefs frameshift NM_001408439.1:c.1592_1595delTAAC NP_001395368.1:p.Thr532Ilefs frameshift NM_001408440.1:c.1592_1595delTAAC NP_001395369.1:p.Thr532Ilefs frameshift NM_001408441.1:c.1592_1595delTAAC NP_001395370.1:p.Thr532Ilefs frameshift NM_001408442.1:c.1592_1595delTAAC NP_001395371.1:p.Thr532Ilefs frameshift NM_001408443.1:c.1592_1595delTAAC NP_001395372.1:p.Thr532Ilefs frameshift NM_001408444.1:c.1592_1595delTAAC NP_001395373.1:p.Thr532Ilefs frameshift NM_001408445.1:c.1589_1592delTAAC NP_001395374.1:p.Thr531Ilefs frameshift NM_001408446.1:c.1589_1592delTAAC NP_001395375.1:p.Thr531Ilefs frameshift NM_001408447.1:c.1589_1592delTAAC NP_001395376.1:p.Thr531Ilefs frameshift NM_001408448.1:c.1589_1592delTAAC NP_001395377.1:p.Thr531Ilefs frameshift NM_001408450.1:c.1589_1592delTAAC NP_001395379.1:p.Thr531Ilefs frameshift NM_001408451.1:c.1583_1586delTAAC NP_001395380.1:p.Thr529Ilefs frameshift NM_001408452.1:c.1577_1580delTAAC NP_001395381.1:p.Thr527Ilefs frameshift NM_001408453.1:c.1577_1580delTAAC NP_001395382.1:p.Thr527Ilefs frameshift NM_001408454.1:c.1577_1580delTAAC NP_001395383.1:p.Thr527Ilefs frameshift NM_001408455.1:c.1577_1580delTAAC NP_001395384.1:p.Thr527Ilefs frameshift NM_001408456.1:c.1577_1580delTAAC NP_001395385.1:p.Thr527Ilefs frameshift NM_001408457.1:c.1577_1580delTAAC NP_001395386.1:p.Thr527Ilefs frameshift NM_001408458.1:c.1574_1577delTAAC NP_001395387.1:p.Thr526Ilefs frameshift NM_001408459.1:c.1574_1577delTAAC NP_001395388.1:p.Thr526Ilefs frameshift NM_001408460.1:c.1574_1577delTAAC NP_001395389.1:p.Thr526Ilefs frameshift NM_001408461.1:c.1574_1577delTAAC NP_001395390.1:p.Thr526Ilefs frameshift NM_001408462.1:c.1574_1577delTAAC NP_001395391.1:p.Thr526Ilefs frameshift NM_001408463.1:c.1574_1577delTAAC NP_001395392.1:p.Thr526Ilefs frameshift NM_001408464.1:c.1574_1577delTAAC NP_001395393.1:p.Thr526Ilefs frameshift NM_001408465.1:c.1574_1577delTAAC NP_001395394.1:p.Thr526Ilefs frameshift NM_001408466.1:c.1574_1577delTAAC NP_001395395.1:p.Thr526Ilefs frameshift NM_001408467.1:c.1574_1577delTAAC NP_001395396.1:p.Thr526Ilefs frameshift NM_001408468.1:c.1571_1574delTAAC NP_001395397.1:p.Thr525Ilefs frameshift NM_001408469.1:c.1571_1574delTAAC NP_001395398.1:p.Thr525Ilefs frameshift NM_001408470.1:c.1571_1574delTAAC NP_001395399.1:p.Thr525Ilefs frameshift NM_001408472.1:c.1715_1718delTAAC NP_001395401.1:p.Thr573Ilefs frameshift NM_001408473.1:c.1712_1715delTAAC NP_001395402.1:p.Thr572Ilefs frameshift NM_001408474.1:c.1517_1520delTAAC NP_001395403.1:p.Thr507Ilefs frameshift NM_001408475.1:c.1514_1517delTAAC NP_001395404.1:p.Thr506Ilefs frameshift NM_001408476.1:c.1514_1517delTAAC NP_001395405.1:p.Thr506Ilefs frameshift NM_001408478.1:c.1508_1511delTAAC NP_001395407.1:p.Thr504Ilefs frameshift NM_001408479.1:c.1508_1511delTAAC NP_001395408.1:p.Thr504Ilefs frameshift NM_001408480.1:c.1508_1511delTAAC NP_001395409.1:p.Thr504Ilefs frameshift NM_001408481.1:c.1505_1508delTAAC NP_001395410.1:p.Thr503Ilefs frameshift NM_001408482.1:c.1505_1508delTAAC NP_001395411.1:p.Thr503Ilefs frameshift NM_001408483.1:c.1505_1508delTAAC NP_001395412.1:p.Thr503Ilefs frameshift NM_001408484.1:c.1505_1508delTAAC NP_001395413.1:p.Thr503Ilefs frameshift NM_001408485.1:c.1505_1508delTAAC NP_001395414.1:p.Thr503Ilefs frameshift NM_001408489.1:c.1505_1508delTAAC NP_001395418.1:p.Thr503Ilefs frameshift NM_001408490.1:c.1505_1508delTAAC NP_001395419.1:p.Thr503Ilefs frameshift NM_001408491.1:c.1505_1508delTAAC NP_001395420.1:p.Thr503Ilefs frameshift NM_001408492.1:c.1502_1505delTAAC NP_001395421.1:p.Thr502Ilefs frameshift NM_001408493.1:c.1502_1505delTAAC NP_001395422.1:p.Thr502Ilefs frameshift NM_001408494.1:c.1478_1481delTAAC NP_001395423.1:p.Thr494Ilefs frameshift NM_001408495.1:c.1472_1475delTAAC NP_001395424.1:p.Thr492Ilefs frameshift NM_001408496.1:c.1454_1457delTAAC NP_001395425.1:p.Thr486Ilefs frameshift NM_001408497.1:c.1454_1457delTAAC NP_001395426.1:p.Thr486Ilefs frameshift NM_001408498.1:c.1454_1457delTAAC NP_001395427.1:p.Thr486Ilefs frameshift NM_001408499.1:c.1454_1457delTAAC NP_001395428.1:p.Thr486Ilefs frameshift NM_001408500.1:c.1454_1457delTAAC NP_001395429.1:p.Thr486Ilefs frameshift NM_001408501.1:c.1454_1457delTAAC NP_001395430.1:p.Thr486Ilefs frameshift NM_001408502.1:c.1451_1454delTAAC NP_001395431.1:p.Thr485Ilefs frameshift NM_001408503.1:c.1451_1454delTAAC NP_001395432.1:p.Thr485Ilefs frameshift NM_001408504.1:c.1451_1454delTAAC NP_001395433.1:p.Thr485Ilefs frameshift NM_001408505.1:c.1448_1451delTAAC NP_001395434.1:p.Thr484Ilefs frameshift NM_001408506.1:c.1391_1394delTAAC NP_001395435.1:p.Thr465Ilefs frameshift NM_001408507.1:c.1388_1391delTAAC NP_001395436.1:p.Thr464Ilefs frameshift NM_001408508.1:c.1379_1382delTAAC NP_001395437.1:p.Thr461Ilefs frameshift NM_001408509.1:c.1376_1379delTAAC NP_001395438.1:p.Thr460Ilefs frameshift NM_001408510.1:c.1337_1340delTAAC NP_001395439.1:p.Thr447Ilefs frameshift NM_001408511.1:c.1334_1337delTAAC NP_001395440.1:p.Thr446Ilefs frameshift NM_001408512.1:c.1214_1217delTAAC NP_001395441.1:p.Thr406Ilefs frameshift NM_001408513.1:c.1187_1190delTAAC NP_001395442.1:p.Thr397Ilefs frameshift NM_007294.3:c.5030_5033delCTAA frameshift NM_007297.4:c.4889_4892del NP_009228.2:p.Thr1630fs frameshift NM_007298.4:c.1715_1718delTAAC NP_009229.2:p.Thr573Ilefs frameshift NM_007299.4:c.1718_1721del NP_009230.2:p.Thr573fs frameshift NM_007300.3:c.5090_5093del NM_007300.4:c.5093_5096del NP_009231.2:p.Thr1698fs frameshift NM_007304.2:c.1715_1718delTAAC NP_009235.2:p.Thr573Ilefs frameshift NR_027676.2:n.5207_5210del non-coding transcript variant NC_000017.11:g.43067652_43067655del NC_000017.10:g.41219669_41219672del NG_005905.2:g.150332_150335del LRG_292:g.150332_150335del LRG_292t1:c.5027_5030del LRG_292p1:p.Thr1677Ilefs U14680.1:n.5149_5152delCTAA - Protein change
- T1677fs, T1630fs, T1698fs, T573fs
- Other names
-
5147del4
5146del4
5149del4
- Canonical SPDI
- NC_000017.11:43067648:TTAGTTA:TTA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13044 | 14850 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (12) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000031204.30 | |
| Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Nov 6, 2023 | RCV000236835.23 | |
| Pathogenic (1) |
no assertion criteria provided
|
Nov 4, 2013 | RCV000735512.9 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Dec 8, 2023 | RCV000048741.28 | |
| Pathogenic (1) |
no assertion criteria provided
|
Jul 1, 2021 | RCV003162264.8 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 13, 2023 | RCV000162882.19 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV001353650.10 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 18, 2021 | RCV002490431.8 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV002513283.8 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 1, 2015 | RCV000240792.9 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Sep 08, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000300187.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Nov 03, 2014)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000195936.1
First in ClinVar: May 06, 2016 Last updated: May 06, 2016 |
Tissue: Blood
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Pathogenic
(Nov 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002792367.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076754.13
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Thr1677Ilefs*2) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Thr1677Ilefs*2) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer, and pancreatic cancer (PMID: 9150149, 21989927, 22144684, 22160602). This variant is also known as 5149del4, ter1678 and c.5149delCTAA. ClinVar contains an entry for this variant (Variation ID: 37623). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004563523.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The BRCA1 c.5030_5033del; p.Thr1677IlefsTer2 variant (rs80357580), also known as 5149del4 or c.5149delCTAA, is reported in the literature in many individuals affected with breast and/or ovarian … (more)
The BRCA1 c.5030_5033del; p.Thr1677IlefsTer2 variant (rs80357580), also known as 5149del4 or c.5149delCTAA, is reported in the literature in many individuals affected with breast and/or ovarian cancer, and is reported as a founder variant in the French population (selected publications: Caputo 2012, Guindalini 2022, Kechin 2023, Li 2019, Stoppa-Lyonnet 1997). This variant is also reported in ClinVar (Variation ID: 37623), but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Caputo S et al. Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases. Nucleic Acids Res. 2012 Jan;40(Database issue):D992-1002. PMID: 22144684. Guindalini RSC et al. Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. Sci Rep. 2022 Mar 9;12(1):4190. PMID: 35264596. Kechin A et al. A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia. Breast Cancer Res Treat. 2023 Jan;197(2):387-395. PMID: 36367610. Li JY et al. Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. Int J Cancer. 2019 Jan 15;144(2):281-289. PMID: 29752822. Stoppa-Lyonnet D et al. BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. Am J Hum Genet. 1997 May;60(5):1021-30. PMID: 9150149. (less)
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Pathogenic
(Apr 18, 2016)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564386.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 1
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Pathogenic
(Jun 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000785273.2
First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
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Pathogenic
(Jul 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV000839222.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(Aug 09, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296478.6
First in ClinVar: May 06, 2016 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In addition, it … (more)
This frameshift variant causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In addition, it has been reported in affected individuals with breast and/or ovarian cancer and has been reported as a founder variant in French breast cancer populations (PMIDs: 31372034 (2019), 30128899 (2018), 29907814 (2018), 22144684 (2012), and 9150149 (1997)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Nov 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004212753.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Nov 01, 2015)
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criteria provided, single submitter
Method: research
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Breast neoplasm
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University
Additional submitter:
Asia and Emerging Markets iMed, AstraZeneca
Accession: SCV000265866.1
First in ClinVar: Sep 14, 2016 Last updated: Sep 14, 2016 |
Number of individuals with the variant: 1
Geographic origin: China
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Pathogenic
(Sep 21, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744603.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446761.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Breast carcinoma (present)
Sex: female
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Biomedical Genomics and Oncogenetics Laboratory, Institut Pasteur de Tunis, University Tunis El Manar
Accession: SCV001519672.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Number of individuals with the variant: 1
Age: 40-49 years
Sex: female
Geographic origin: Tunisia
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Pathogenic
(Mar 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916746.2
First in ClinVar: Jun 03, 2019 Last updated: Apr 23, 2022 |
Comment:
Variant summary: BRCA1 c.5030_5033delCTAA (p.Thr1677IlefsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.5030_5033delCTAA (p.Thr1677IlefsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251382 control chromosomes. c.5030_5033delCTAA has been reported in the literature in numerous individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. 13 clinical submitters via ClinVar have classified the variant as pathogenic, including an expert panel. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326110.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Apr 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000292525.14
First in ClinVar: Jul 24, 2016 Last updated: Apr 23, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Stoppa-Lyonnet et al., 1997; Schneegans et al., 2012; Solano et al., 2012; de Juan Jimenez et al., 2013; Kang et al., 2015; Rweyemamu et al., 2023); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5149_5152delCTAA; This variant is associated with the following publications: (PMID: 28127413, 22160602, 25863477, 30702160, 30287823, 34290354, 34490083, 34413315, 32455662, 32980694, 32772980, 32438681, 30040829, 28888541, 9150149, 22144684, 21989927, 23961350, 23479189, 26183948, 24916970, 15146557, 26843898, 26083025, 27741520, 22798144, 27553291, 27062684, 29020732, 29339979, 29752822, 28831036, 29907814, 28111427, 31372034, 30309222, 30199306, 32072338, 29625052, 26689913, 33726785, 11597388, 32341426, 32719484, 30875412, 30787465, 30613976, 36139606, 34645131, 35264596, 34063308, 34072659, 36230495, 33403015, 32245699, 32380732, 35908255, 35451682, 35893033, 34657357, 35216584, 33649982, 32694901, 34022715, 32862574) (less)
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Pathogenic
(Oct 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004224816.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP5, PM2, PS4_moderate, PVS1
Number of individuals with the variant: 1
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Pathogenic
(Nov 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000683243.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 4 nucleotides in exon 16 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 4 nucleotides in exon 16 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 11 individuals affected with breast and/or ovarian cancer (PMID: 22160602, 22798144, 23961350, 23479189, 24916970, 25863477, 29339979, 29409476, 29752822, 29907814, 30128899, 33471991). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Apr 03, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004808356.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
Comment:
This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as … (more)
This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer, and pancreatic cancer (PMID: 9150149, 21989927, 22144684, 22160602). This variant is also known as 5149del4, ter1678 and c.5149delCTAA. ClinVar contains an entry for this variant (Variation ID: 37623). For these reasons, this variant has been classified as Pathogenic. (less)
Age: 40-49 years
Sex: female
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Pathogenic
(May 06, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000213369.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The c.5030_5033delCTAA pathogenic mutation, located in coding exon 15 of the BRCA1 gene, results from a deletion of 4 nucleotides at positions 5030 to 5033, … (more)
The c.5030_5033delCTAA pathogenic mutation, located in coding exon 15 of the BRCA1 gene, results from a deletion of 4 nucleotides at positions 5030 to 5033, causing a translational frameshift with a predicted alternate stop codon (p.T1677Ifs*2). This mutation has been reported in numerous HBOC families and patients with triple negative breast cancer throughout the world (Stoppa-Lyonnet D et al. Am. J. Hum. Genet. 1997 May;60(5):1021-30; Caputo S et al. Nucleic Acids Res. 2012 Jan;40(Database issue):D992-1002; Ghiorzo P et al. Fam. Cancer 2012 Mar;11(1):41-7; Schneegans SM et al. Fam. Cancer 2012 Jun;11(2):181-8; Kim H et al. Breast Cancer Res. Treat. 2012 Aug;134(3):1315-26; Kang E et al. Breast Cancer Res. Treat. 2015 May;151(1):157-68; Dodova RI et al. BMC Cancer 2015 Jul;15:523; Rashid M et al. BMC Cancer 2016 08;16(1):673; Heramb C et al. Hered. Cancer Clin. Pract. 2018 Jan;16:3; Abdel-Razeq H et al. BMC Cancer 2018 02;18(1):152). Of note, this alteration is also designated as 5149del4 and 5149delCTAA in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Nov 04, 2013)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863650.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
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Pathogenic
(May 01, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000053804.5
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587444.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591562.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Thr1677IlefsX2 deletion variant was identified in 39 of 56694 proband chromosomes (frequency: 0.001) from individuals with breast or ovarian cancer (Caputo 2011, Ghiorzo 2012, … (more)
The p.Thr1677IlefsX2 deletion variant was identified in 39 of 56694 proband chromosomes (frequency: 0.001) from individuals with breast or ovarian cancer (Caputo 2011, Ghiorzo 2012, Solano 2012, Stoppa-Lyonnet 1997, van der Hout 2006). This variant was also identified in the following databases: dbSNP (ID: rs80357862) “With pathogenic allele”, LOVD, UMD (59X as a causal variant), and BIC (17X with clinical importance). The p.Thr1677IlefsX2 variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1677 and leads to a premature stop codon at position 1678. This alteration is then predicted to result in a truncated or absent protein and loss of function, and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145266.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 401
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 3:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian
Geographic origin: France
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 5:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 6:
Number of individuals with the variant: 5
Ethnicity/Population group: Western European
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001739788.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001905851.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
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Pathogenic
(Aug 26, 2022)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV002588820.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758466.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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Research and Experiment Center, Meizhou People's Hospital
Accession: SCV003760906.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Sex: female
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Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Thr1677Ilefs*2) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer, and pancreatic cancer (PMID: 9150149, 21989927, 22144684, 22160602). This variant is also known as 5149del4, ter1678 and c.5149delCTAA. ClinVar contains an entry for this variant (Variation ID: 37623). For these reasons, this variant has been classified as Pathogenic.
Comment:
The BRCA1 c.5030_5033del; p.Thr1677IlefsTer2 variant (rs80357580), also known as 5149del4 or c.5149delCTAA, is reported in the literature in many individuals affected with breast and/or ovarian cancer, and is reported as a founder variant in the French population (selected publications: Caputo 2012, Guindalini 2022, Kechin 2023, Li 2019, Stoppa-Lyonnet 1997). This variant is also reported in ClinVar (Variation ID: 37623), but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Caputo S et al. Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases. Nucleic Acids Res. 2012 Jan;40(Database issue):D992-1002. PMID: 22144684. Guindalini RSC et al. Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. Sci Rep. 2022 Mar 9;12(1):4190. PMID: 35264596. Kechin A et al. A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia. Breast Cancer Res Treat. 2023 Jan;197(2):387-395. PMID: 36367610. Li JY et al. Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. Int J Cancer. 2019 Jan 15;144(2):281-289. PMID: 29752822. Stoppa-Lyonnet D et al. BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. Am J Hum Genet. 1997 May;60(5):1021-30. PMID: 9150149.
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In addition, it has been reported in affected individuals with breast and/or ovarian cancer and has been reported as a founder variant in French breast cancer populations (PMIDs: 31372034 (2019), 30128899 (2018), 29907814 (2018), 22144684 (2012), and 9150149 (1997)). Based on the available information, this variant is classified as pathogenic.
Comment:
Variant summary: BRCA1 c.5030_5033delCTAA (p.Thr1677IlefsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251382 control chromosomes. c.5030_5033delCTAA has been reported in the literature in numerous individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. 13 clinical submitters via ClinVar have classified the variant as pathogenic, including an expert panel. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Stoppa-Lyonnet et al., 1997; Schneegans et al., 2012; Solano et al., 2012; de Juan Jimenez et al., 2013; Kang et al., 2015; Rweyemamu et al., 2023); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5149_5152delCTAA; This variant is associated with the following publications: (PMID: 28127413, 22160602, 25863477, 30702160, 30287823, 34290354, 34490083, 34413315, 32455662, 32980694, 32772980, 32438681, 30040829, 28888541, 9150149, 22144684, 21989927, 23961350, 23479189, 26183948, 24916970, 15146557, 26843898, 26083025, 27741520, 22798144, 27553291, 27062684, 29020732, 29339979, 29752822, 28831036, 29907814, 28111427, 31372034, 30309222, 30199306, 32072338, 29625052, 26689913, 33726785, 11597388, 32341426, 32719484, 30875412, 30787465, 30613976, 36139606, 34645131, 35264596, 34063308, 34072659, 36230495, 33403015, 32245699, 32380732, 35908255, 35451682, 35893033, 34657357, 35216584, 33649982, 32694901, 34022715, 32862574)
Comment:
PP5, PM2, PS4_moderate, PVS1
Comment:
This variant deletes 4 nucleotides in exon 16 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 11 individuals affected with breast and/or ovarian cancer (PMID: 22160602, 22798144, 23961350, 23479189, 24916970, 25863477, 29339979, 29409476, 29752822, 29907814, 30128899, 33471991). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer, and pancreatic cancer (PMID: 9150149, 21989927, 22144684, 22160602). This variant is also known as 5149del4, ter1678 and c.5149delCTAA. ClinVar contains an entry for this variant (Variation ID: 37623). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.5030_5033delCTAA pathogenic mutation, located in coding exon 15 of the BRCA1 gene, results from a deletion of 4 nucleotides at positions 5030 to 5033, causing a translational frameshift with a predicted alternate stop codon (p.T1677Ifs*2). This mutation has been reported in numerous HBOC families and patients with triple negative breast cancer throughout the world (Stoppa-Lyonnet D et al. Am. J. Hum. Genet. 1997 May;60(5):1021-30; Caputo S et al. Nucleic Acids Res. 2012 Jan;40(Database issue):D992-1002; Ghiorzo P et al. Fam. Cancer 2012 Mar;11(1):41-7; Schneegans SM et al. Fam. Cancer 2012 Jun;11(2):181-8; Kim H et al. Breast Cancer Res. Treat. 2012 Aug;134(3):1315-26; Kang E et al. Breast Cancer Res. Treat. 2015 May;151(1):157-68; Dodova RI et al. BMC Cancer 2015 Jul;15:523; Rashid M et al. BMC Cancer 2016 08;16(1):673; Heramb C et al. Hered. Cancer Clin. Pract. 2018 Jan;16:3; Abdel-Razeq H et al. BMC Cancer 2018 02;18(1):152). Of note, this alteration is also designated as 5149del4 and 5149delCTAA in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
The p.Thr1677IlefsX2 deletion variant was identified in 39 of 56694 proband chromosomes (frequency: 0.001) from individuals with breast or ovarian cancer (Caputo 2011, Ghiorzo 2012, Solano 2012, Stoppa-Lyonnet 1997, van der Hout 2006). This variant was also identified in the following databases: dbSNP (ID: rs80357862) “With pathogenic allele”, LOVD, UMD (59X as a causal variant), and BIC (17X with clinical importance). The p.Thr1677IlefsX2 variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1677 and leads to a premature stop codon at position 1678. This alteration is then predicted to result in a truncated or absent protein and loss of function, and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
This sequence change creates a premature translational stop signal (p.Thr1677Ilefs*2) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer, and pancreatic cancer (PMID: 9150149, 21989927, 22144684, 22160602). This variant is also known as 5149del4, ter1678 and c.5149delCTAA. ClinVar contains an entry for this variant (Variation ID: 37623). For these reasons, this variant has been classified as Pathogenic.
Comment:
The BRCA1 c.5030_5033del; p.Thr1677IlefsTer2 variant (rs80357580), also known as 5149del4 or c.5149delCTAA, is reported in the literature in many individuals affected with breast and/or ovarian cancer, and is reported as a founder variant in the French population (selected publications: Caputo 2012, Guindalini 2022, Kechin 2023, Li 2019, Stoppa-Lyonnet 1997). This variant is also reported in ClinVar (Variation ID: 37623), but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Caputo S et al. Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases. Nucleic Acids Res. 2012 Jan;40(Database issue):D992-1002. PMID: 22144684. Guindalini RSC et al. Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. Sci Rep. 2022 Mar 9;12(1):4190. PMID: 35264596. Kechin A et al. A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia. Breast Cancer Res Treat. 2023 Jan;197(2):387-395. PMID: 36367610. Li JY et al. Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. Int J Cancer. 2019 Jan 15;144(2):281-289. PMID: 29752822. Stoppa-Lyonnet D et al. BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. Am J Hum Genet. 1997 May;60(5):1021-30. PMID: 9150149.
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In addition, it has been reported in affected individuals with breast and/or ovarian cancer and has been reported as a founder variant in French breast cancer populations (PMIDs: 31372034 (2019), 30128899 (2018), 29907814 (2018), 22144684 (2012), and 9150149 (1997)). Based on the available information, this variant is classified as pathogenic.
Comment:
Variant summary: BRCA1 c.5030_5033delCTAA (p.Thr1677IlefsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251382 control chromosomes. c.5030_5033delCTAA has been reported in the literature in numerous individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. 13 clinical submitters via ClinVar have classified the variant as pathogenic, including an expert panel. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Stoppa-Lyonnet et al., 1997; Schneegans et al., 2012; Solano et al., 2012; de Juan Jimenez et al., 2013; Kang et al., 2015; Rweyemamu et al., 2023); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5149_5152delCTAA; This variant is associated with the following publications: (PMID: 28127413, 22160602, 25863477, 30702160, 30287823, 34290354, 34490083, 34413315, 32455662, 32980694, 32772980, 32438681, 30040829, 28888541, 9150149, 22144684, 21989927, 23961350, 23479189, 26183948, 24916970, 15146557, 26843898, 26083025, 27741520, 22798144, 27553291, 27062684, 29020732, 29339979, 29752822, 28831036, 29907814, 28111427, 31372034, 30309222, 30199306, 32072338, 29625052, 26689913, 33726785, 11597388, 32341426, 32719484, 30875412, 30787465, 30613976, 36139606, 34645131, 35264596, 34063308, 34072659, 36230495, 33403015, 32245699, 32380732, 35908255, 35451682, 35893033, 34657357, 35216584, 33649982, 32694901, 34022715, 32862574)
Comment:
PP5, PM2, PS4_moderate, PVS1
Comment:
This variant deletes 4 nucleotides in exon 16 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 11 individuals affected with breast and/or ovarian cancer (PMID: 22160602, 22798144, 23961350, 23479189, 24916970, 25863477, 29339979, 29409476, 29752822, 29907814, 30128899, 33471991). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer, and pancreatic cancer (PMID: 9150149, 21989927, 22144684, 22160602). This variant is also known as 5149del4, ter1678 and c.5149delCTAA. ClinVar contains an entry for this variant (Variation ID: 37623). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.5030_5033delCTAA pathogenic mutation, located in coding exon 15 of the BRCA1 gene, results from a deletion of 4 nucleotides at positions 5030 to 5033, causing a translational frameshift with a predicted alternate stop codon (p.T1677Ifs*2). This mutation has been reported in numerous HBOC families and patients with triple negative breast cancer throughout the world (Stoppa-Lyonnet D et al. Am. J. Hum. Genet. 1997 May;60(5):1021-30; Caputo S et al. Nucleic Acids Res. 2012 Jan;40(Database issue):D992-1002; Ghiorzo P et al. Fam. Cancer 2012 Mar;11(1):41-7; Schneegans SM et al. Fam. Cancer 2012 Jun;11(2):181-8; Kim H et al. Breast Cancer Res. Treat. 2012 Aug;134(3):1315-26; Kang E et al. Breast Cancer Res. Treat. 2015 May;151(1):157-68; Dodova RI et al. BMC Cancer 2015 Jul;15:523; Rashid M et al. BMC Cancer 2016 08;16(1):673; Heramb C et al. Hered. Cancer Clin. Pract. 2018 Jan;16:3; Abdel-Razeq H et al. BMC Cancer 2018 02;18(1):152). Of note, this alteration is also designated as 5149del4 and 5149delCTAA in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
The p.Thr1677IlefsX2 deletion variant was identified in 39 of 56694 proband chromosomes (frequency: 0.001) from individuals with breast or ovarian cancer (Caputo 2011, Ghiorzo 2012, Solano 2012, Stoppa-Lyonnet 1997, van der Hout 2006). This variant was also identified in the following databases: dbSNP (ID: rs80357862) “With pathogenic allele”, LOVD, UMD (59X as a causal variant), and BIC (17X with clinical importance). The p.Thr1677IlefsX2 variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1677 and leads to a premature stop codon at position 1678. This alteration is then predicted to result in a truncated or absent protein and loss of function, and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
| Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia. | Ben Ayed-Guerfali D | Journal of translational medicine | 2021 | PMID: 33726785 |
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer? | Nguyen-Dumont T | Genetics research | 2020 | PMID: 32772980 |
| Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
| Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. | De Talhouet S | Scientific reports | 2020 | PMID: 32341426 |
| The spectrum of BRCA1 and BRCA2 mutations and clinicopathological characteristics in Chinese women with early-onset breast cancer. | Chen L | Breast cancer research and treatment | 2020 | PMID: 32072338 |
| Frequency of germline mutations in BRCA1 and BRCA2 in ovarian cancer patients and their effect on treatment outcome. | Ashour M | Cancer management and research | 2019 | PMID: 31372034 |
| Discoveries beyond BRCA1/2: Multigene testing in an Asian multi-ethnic cohort suspected of hereditary breast cancer syndrome in the real world. | Ow SGW | PloS one | 2019 | PMID: 30875412 |
| Toward automation of germline variant curation in clinical cancer genetics. | Ravichandran V | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 30787465 |
| Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
| Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy. | Rizzolo P | International journal of cancer | 2019 | PMID: 30613976 |
| Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review. | Kwon BS | Cancer research and treatment | 2019 | PMID: 30309222 |
| Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
| Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
| Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer. | Abulkhair O | Journal of global oncology | 2018 | PMID: 30199306 |
| BRCA Mutation Status to Personalize Management of Recurrent Ovarian Cancer: A Multicenter Study. | Marchetti C | Annals of surgical oncology | 2018 | PMID: 30128899 |
| BRCA1 founder mutations and beyond in the Polish population: A single-institution BRCA1/2 next-generation sequencing study. | Kowalik A | PloS one | 2018 | PMID: 30040829 |
| The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
| Pathogenic Germline Variants in 10,389 Adult Cancers. | Huang KL | Cell | 2018 | PMID: 29625052 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan. | Abdel-Razeq H | BMC cancer | 2018 | PMID: 29409476 |
| BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
| Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2. | Eoh KJ | Cancer research and treatment | 2018 | PMID: 29020732 |
| BRCA locus-specific loss of heterozygosity in germline BRCA1 and BRCA2 carriers. | Maxwell KN | Nature communications | 2017 | PMID: 28831036 |
| Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls. | Park JS | Cancer research and treatment | 2017 | PMID: 28111427 |
| Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry. | Fernandes GC | Oncotarget | 2016 | PMID: 27741520 |
| High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients. | Rashid MU | BMC cancer | 2016 | PMID: 27553291 |
| Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients. | Zhong X | PloS one | 2016 | PMID: 27257965 |
| Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families: A monocentric Italian study. | Azzollini J | European journal of internal medicine | 2016 | PMID: 27062684 |
| Patterns and functional implications of rare germline variants across 12 cancer types. | Lu C | Nature communications | 2015 | PMID: 26689913 |
| Spectrum and frequencies of BRCA1/2 mutations in Bulgarian high risk breast cancer patients. | Dodova RI | BMC cancer | 2015 | PMID: 26183948 |
| Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers. | Domagala P | PloS one | 2015 | PMID: 26083025 |
| The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study. | Kang E | Breast cancer research and treatment | 2015 | PMID: 25863477 |
| Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. | Wong-Brown MW | Breast cancer research and treatment | 2015 | PMID: 25682074 |
| The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian cancer families of Portuguese ancestry. | Peixoto A | Clinical genetics | 2015 | PMID: 24916970 |
| Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence. | de Juan Jiménez I | Familial cancer | 2013 | PMID: 23479189 |
| BRCA1 And BRCA2 analysis of Argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin. | Solano AR | SpringerPlus | 2012 | PMID: 23961350 |
| Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. | Kim H | Breast cancer research and treatment | 2012 | PMID: 22798144 |
| Multimodel assessment of BRCA1 mutations in Taiwanese (ethnic Chinese) women with early-onset, bilateral or familial breast cancer. | Kuo WH | Journal of human genetics | 2012 | PMID: 22277901 |
| Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. | Schneegans SM | Familial cancer | 2012 | PMID: 22160602 |
| Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases. | Caputo S | Nucleic acids research | 2012 | PMID: 22144684 |
| Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy. | Ghiorzo P | Familial cancer | 2012 | PMID: 21989927 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern Italy (Sicily): a mutation analyses. | Russo A | Breast cancer research and treatment | 2007 | PMID: 17221156 |
| A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. | van der Hout AH | Human mutation | 2006 | PMID: 16683254 |
| Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations. | Marroni F | European journal of human genetics : EJHG | 2004 | PMID: 15340362 |
| A high proportion of founder BRCA1 mutations in Polish breast cancer families. | Górski B | International journal of cancer | 2004 | PMID: 15146557 |
| Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families. | Verhoog LC | European journal of cancer (Oxford, England : 1990) | 2001 | PMID: 11597388 |
| BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. | Stoppa-Lyonnet D | American journal of human genetics | 1997 | PMID: 9150149 |
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Text-mined citations for rs80357580 ...
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the rs number, so they may include citations for more than one variant
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Record last updated Nov 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.