ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1723G>A (p.Glu575Lys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(7); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.1723G>A (p.Glu575Lys)
Variation ID: 54334 Accession: VCV000054334.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093808 (GRCh38) [ NCBI UCSC ] 17: 41245825 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Sep 28, 2017 May 1, 2024 Nov 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.1723G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu575Lys missense NM_001407571.1:c.1510G>A NP_001394500.1:p.Glu504Lys missense NM_001407581.1:c.1723G>A NP_001394510.1:p.Glu575Lys missense NM_001407582.1:c.1723G>A NP_001394511.1:p.Glu575Lys missense NM_001407583.1:c.1723G>A NP_001394512.1:p.Glu575Lys missense NM_001407585.1:c.1723G>A NP_001394514.1:p.Glu575Lys missense NM_001407587.1:c.1720G>A NP_001394516.1:p.Glu574Lys missense NM_001407590.1:c.1720G>A NP_001394519.1:p.Glu574Lys missense NM_001407591.1:c.1720G>A NP_001394520.1:p.Glu574Lys missense NM_001407593.1:c.1723G>A NP_001394522.1:p.Glu575Lys missense NM_001407594.1:c.1723G>A NP_001394523.1:p.Glu575Lys missense NM_001407596.1:c.1723G>A NP_001394525.1:p.Glu575Lys missense NM_001407597.1:c.1723G>A NP_001394526.1:p.Glu575Lys missense NM_001407598.1:c.1723G>A NP_001394527.1:p.Glu575Lys missense NM_001407602.1:c.1723G>A NP_001394531.1:p.Glu575Lys missense NM_001407603.1:c.1723G>A NP_001394532.1:p.Glu575Lys missense NM_001407605.1:c.1723G>A NP_001394534.1:p.Glu575Lys missense NM_001407610.1:c.1720G>A NP_001394539.1:p.Glu574Lys missense NM_001407611.1:c.1720G>A NP_001394540.1:p.Glu574Lys missense NM_001407612.1:c.1720G>A NP_001394541.1:p.Glu574Lys missense NM_001407613.1:c.1720G>A NP_001394542.1:p.Glu574Lys missense NM_001407614.1:c.1720G>A NP_001394543.1:p.Glu574Lys missense NM_001407615.1:c.1720G>A NP_001394544.1:p.Glu574Lys missense NM_001407616.1:c.1723G>A NP_001394545.1:p.Glu575Lys missense NM_001407617.1:c.1723G>A NP_001394546.1:p.Glu575Lys missense NM_001407618.1:c.1723G>A NP_001394547.1:p.Glu575Lys missense NM_001407619.1:c.1723G>A NP_001394548.1:p.Glu575Lys missense NM_001407620.1:c.1723G>A NP_001394549.1:p.Glu575Lys missense NM_001407621.1:c.1723G>A NP_001394550.1:p.Glu575Lys missense NM_001407622.1:c.1723G>A NP_001394551.1:p.Glu575Lys missense NM_001407623.1:c.1723G>A NP_001394552.1:p.Glu575Lys missense NM_001407624.1:c.1723G>A NP_001394553.1:p.Glu575Lys missense NM_001407625.1:c.1723G>A NP_001394554.1:p.Glu575Lys missense NM_001407626.1:c.1723G>A NP_001394555.1:p.Glu575Lys missense NM_001407627.1:c.1720G>A NP_001394556.1:p.Glu574Lys missense NM_001407628.1:c.1720G>A NP_001394557.1:p.Glu574Lys missense NM_001407629.1:c.1720G>A NP_001394558.1:p.Glu574Lys missense NM_001407630.1:c.1720G>A NP_001394559.1:p.Glu574Lys missense NM_001407631.1:c.1720G>A NP_001394560.1:p.Glu574Lys missense NM_001407632.1:c.1720G>A NP_001394561.1:p.Glu574Lys missense NM_001407633.1:c.1720G>A NP_001394562.1:p.Glu574Lys missense NM_001407634.1:c.1720G>A NP_001394563.1:p.Glu574Lys missense NM_001407635.1:c.1720G>A NP_001394564.1:p.Glu574Lys missense NM_001407636.1:c.1720G>A NP_001394565.1:p.Glu574Lys missense NM_001407637.1:c.1720G>A NP_001394566.1:p.Glu574Lys missense NM_001407638.1:c.1720G>A NP_001394567.1:p.Glu574Lys missense NM_001407639.1:c.1723G>A NP_001394568.1:p.Glu575Lys missense NM_001407640.1:c.1723G>A NP_001394569.1:p.Glu575Lys missense NM_001407641.1:c.1723G>A NP_001394570.1:p.Glu575Lys missense NM_001407642.1:c.1723G>A NP_001394571.1:p.Glu575Lys missense NM_001407644.1:c.1720G>A NP_001394573.1:p.Glu574Lys missense NM_001407645.1:c.1720G>A NP_001394574.1:p.Glu574Lys missense NM_001407646.1:c.1714G>A NP_001394575.1:p.Glu572Lys missense NM_001407647.1:c.1714G>A NP_001394576.1:p.Glu572Lys missense NM_001407648.1:c.1600G>A NP_001394577.1:p.Glu534Lys missense NM_001407649.1:c.1597G>A NP_001394578.1:p.Glu533Lys missense NM_001407652.1:c.1723G>A NP_001394581.1:p.Glu575Lys missense NM_001407653.1:c.1645G>A NP_001394582.1:p.Glu549Lys missense NM_001407654.1:c.1645G>A NP_001394583.1:p.Glu549Lys missense NM_001407655.1:c.1645G>A NP_001394584.1:p.Glu549Lys missense NM_001407656.1:c.1645G>A NP_001394585.1:p.Glu549Lys missense NM_001407657.1:c.1645G>A NP_001394586.1:p.Glu549Lys missense NM_001407658.1:c.1645G>A NP_001394587.1:p.Glu549Lys missense NM_001407659.1:c.1642G>A NP_001394588.1:p.Glu548Lys missense NM_001407660.1:c.1642G>A NP_001394589.1:p.Glu548Lys missense NM_001407661.1:c.1642G>A NP_001394590.1:p.Glu548Lys missense NM_001407662.1:c.1642G>A NP_001394591.1:p.Glu548Lys missense NM_001407663.1:c.1645G>A NP_001394592.1:p.Glu549Lys missense NM_001407664.1:c.1600G>A NP_001394593.1:p.Glu534Lys missense NM_001407665.1:c.1600G>A NP_001394594.1:p.Glu534Lys missense NM_001407666.1:c.1600G>A NP_001394595.1:p.Glu534Lys missense NM_001407667.1:c.1600G>A NP_001394596.1:p.Glu534Lys missense NM_001407668.1:c.1600G>A NP_001394597.1:p.Glu534Lys missense NM_001407669.1:c.1600G>A NP_001394598.1:p.Glu534Lys missense NM_001407670.1:c.1597G>A NP_001394599.1:p.Glu533Lys missense NM_001407671.1:c.1597G>A NP_001394600.1:p.Glu533Lys missense NM_001407672.1:c.1597G>A NP_001394601.1:p.Glu533Lys missense NM_001407673.1:c.1597G>A NP_001394602.1:p.Glu533Lys missense NM_001407674.1:c.1600G>A NP_001394603.1:p.Glu534Lys missense NM_001407675.1:c.1600G>A NP_001394604.1:p.Glu534Lys missense NM_001407676.1:c.1600G>A NP_001394605.1:p.Glu534Lys missense NM_001407677.1:c.1600G>A NP_001394606.1:p.Glu534Lys missense NM_001407678.1:c.1600G>A NP_001394607.1:p.Glu534Lys missense NM_001407679.1:c.1600G>A NP_001394608.1:p.Glu534Lys missense NM_001407680.1:c.1600G>A NP_001394609.1:p.Glu534Lys missense NM_001407681.1:c.1600G>A NP_001394610.1:p.Glu534Lys missense NM_001407682.1:c.1600G>A NP_001394611.1:p.Glu534Lys missense NM_001407683.1:c.1600G>A NP_001394612.1:p.Glu534Lys missense NM_001407684.1:c.1723G>A NP_001394613.1:p.Glu575Lys missense NM_001407685.1:c.1597G>A NP_001394614.1:p.Glu533Lys missense NM_001407686.1:c.1597G>A NP_001394615.1:p.Glu533Lys missense NM_001407687.1:c.1597G>A NP_001394616.1:p.Glu533Lys missense NM_001407688.1:c.1597G>A NP_001394617.1:p.Glu533Lys missense NM_001407689.1:c.1597G>A NP_001394618.1:p.Glu533Lys missense NM_001407690.1:c.1597G>A NP_001394619.1:p.Glu533Lys missense NM_001407691.1:c.1597G>A NP_001394620.1:p.Glu533Lys missense NM_001407692.1:c.1582G>A NP_001394621.1:p.Glu528Lys missense NM_001407694.1:c.1582G>A NP_001394623.1:p.Glu528Lys missense NM_001407695.1:c.1582G>A NP_001394624.1:p.Glu528Lys missense NM_001407696.1:c.1582G>A NP_001394625.1:p.Glu528Lys missense NM_001407697.1:c.1582G>A NP_001394626.1:p.Glu528Lys missense NM_001407698.1:c.1582G>A NP_001394627.1:p.Glu528Lys missense NM_001407724.1:c.1582G>A NP_001394653.1:p.Glu528Lys missense NM_001407725.1:c.1582G>A NP_001394654.1:p.Glu528Lys missense NM_001407726.1:c.1582G>A NP_001394655.1:p.Glu528Lys missense NM_001407727.1:c.1582G>A NP_001394656.1:p.Glu528Lys missense NM_001407728.1:c.1582G>A NP_001394657.1:p.Glu528Lys missense NM_001407729.1:c.1582G>A NP_001394658.1:p.Glu528Lys missense NM_001407730.1:c.1582G>A NP_001394659.1:p.Glu528Lys missense NM_001407731.1:c.1582G>A NP_001394660.1:p.Glu528Lys missense NM_001407732.1:c.1582G>A NP_001394661.1:p.Glu528Lys missense NM_001407733.1:c.1582G>A NP_001394662.1:p.Glu528Lys missense NM_001407734.1:c.1582G>A NP_001394663.1:p.Glu528Lys missense NM_001407735.1:c.1582G>A NP_001394664.1:p.Glu528Lys missense NM_001407736.1:c.1582G>A NP_001394665.1:p.Glu528Lys missense NM_001407737.1:c.1582G>A NP_001394666.1:p.Glu528Lys missense NM_001407738.1:c.1582G>A NP_001394667.1:p.Glu528Lys missense NM_001407739.1:c.1582G>A NP_001394668.1:p.Glu528Lys missense NM_001407740.1:c.1579G>A NP_001394669.1:p.Glu527Lys missense NM_001407741.1:c.1579G>A NP_001394670.1:p.Glu527Lys missense NM_001407742.1:c.1579G>A NP_001394671.1:p.Glu527Lys missense NM_001407743.1:c.1579G>A NP_001394672.1:p.Glu527Lys missense NM_001407744.1:c.1579G>A NP_001394673.1:p.Glu527Lys missense NM_001407745.1:c.1579G>A NP_001394674.1:p.Glu527Lys missense NM_001407746.1:c.1579G>A NP_001394675.1:p.Glu527Lys missense NM_001407747.1:c.1579G>A NP_001394676.1:p.Glu527Lys missense NM_001407748.1:c.1579G>A NP_001394677.1:p.Glu527Lys missense NM_001407749.1:c.1579G>A NP_001394678.1:p.Glu527Lys missense NM_001407750.1:c.1582G>A NP_001394679.1:p.Glu528Lys missense NM_001407751.1:c.1582G>A NP_001394680.1:p.Glu528Lys missense NM_001407752.1:c.1582G>A NP_001394681.1:p.Glu528Lys missense NM_001407838.1:c.1579G>A NP_001394767.1:p.Glu527Lys missense NM_001407839.1:c.1579G>A NP_001394768.1:p.Glu527Lys missense NM_001407841.1:c.1579G>A NP_001394770.1:p.Glu527Lys missense NM_001407842.1:c.1579G>A NP_001394771.1:p.Glu527Lys missense NM_001407843.1:c.1579G>A NP_001394772.1:p.Glu527Lys missense NM_001407844.1:c.1579G>A NP_001394773.1:p.Glu527Lys missense NM_001407845.1:c.1579G>A NP_001394774.1:p.Glu527Lys missense NM_001407846.1:c.1579G>A NP_001394775.1:p.Glu527Lys missense NM_001407847.1:c.1579G>A NP_001394776.1:p.Glu527Lys missense NM_001407848.1:c.1579G>A NP_001394777.1:p.Glu527Lys missense NM_001407849.1:c.1579G>A NP_001394778.1:p.Glu527Lys missense NM_001407850.1:c.1582G>A NP_001394779.1:p.Glu528Lys missense NM_001407851.1:c.1582G>A NP_001394780.1:p.Glu528Lys missense NM_001407852.1:c.1582G>A NP_001394781.1:p.Glu528Lys missense NM_001407853.1:c.1510G>A NP_001394782.1:p.Glu504Lys missense NM_001407854.1:c.1723G>A NP_001394783.1:p.Glu575Lys missense NM_001407858.1:c.1723G>A NP_001394787.1:p.Glu575Lys missense NM_001407859.1:c.1723G>A NP_001394788.1:p.Glu575Lys missense NM_001407860.1:c.1720G>A NP_001394789.1:p.Glu574Lys missense NM_001407861.1:c.1720G>A NP_001394790.1:p.Glu574Lys missense NM_001407862.1:c.1522G>A NP_001394791.1:p.Glu508Lys missense NM_001407863.1:c.1600G>A NP_001394792.1:p.Glu534Lys missense NM_001407874.1:c.1519G>A NP_001394803.1:p.Glu507Lys missense NM_001407875.1:c.1519G>A NP_001394804.1:p.Glu507Lys missense NM_001407879.1:c.1513G>A NP_001394808.1:p.Glu505Lys missense NM_001407881.1:c.1513G>A NP_001394810.1:p.Glu505Lys missense NM_001407882.1:c.1513G>A NP_001394811.1:p.Glu505Lys missense NM_001407884.1:c.1513G>A NP_001394813.1:p.Glu505Lys missense NM_001407885.1:c.1513G>A NP_001394814.1:p.Glu505Lys missense NM_001407886.1:c.1513G>A NP_001394815.1:p.Glu505Lys missense NM_001407887.1:c.1513G>A NP_001394816.1:p.Glu505Lys missense NM_001407889.1:c.1513G>A NP_001394818.1:p.Glu505Lys missense NM_001407894.1:c.1510G>A NP_001394823.1:p.Glu504Lys missense NM_001407895.1:c.1510G>A NP_001394824.1:p.Glu504Lys missense NM_001407896.1:c.1510G>A NP_001394825.1:p.Glu504Lys missense NM_001407897.1:c.1510G>A NP_001394826.1:p.Glu504Lys missense NM_001407898.1:c.1510G>A NP_001394827.1:p.Glu504Lys missense NM_001407899.1:c.1510G>A NP_001394828.1:p.Glu504Lys missense NM_001407900.1:c.1513G>A NP_001394829.1:p.Glu505Lys missense NM_001407902.1:c.1513G>A NP_001394831.1:p.Glu505Lys missense NM_001407904.1:c.1513G>A NP_001394833.1:p.Glu505Lys missense NM_001407906.1:c.1513G>A NP_001394835.1:p.Glu505Lys missense NM_001407907.1:c.1513G>A NP_001394836.1:p.Glu505Lys missense NM_001407908.1:c.1513G>A NP_001394837.1:p.Glu505Lys missense NM_001407909.1:c.1513G>A NP_001394838.1:p.Glu505Lys missense NM_001407910.1:c.1513G>A NP_001394839.1:p.Glu505Lys missense NM_001407915.1:c.1510G>A NP_001394844.1:p.Glu504Lys missense NM_001407916.1:c.1510G>A NP_001394845.1:p.Glu504Lys missense NM_001407917.1:c.1510G>A NP_001394846.1:p.Glu504Lys missense NM_001407918.1:c.1510G>A NP_001394847.1:p.Glu504Lys missense NM_001407919.1:c.1600G>A NP_001394848.1:p.Glu534Lys missense NM_001407920.1:c.1459G>A NP_001394849.1:p.Glu487Lys missense NM_001407921.1:c.1459G>A NP_001394850.1:p.Glu487Lys missense NM_001407922.1:c.1459G>A NP_001394851.1:p.Glu487Lys missense NM_001407923.1:c.1459G>A NP_001394852.1:p.Glu487Lys missense NM_001407924.1:c.1459G>A NP_001394853.1:p.Glu487Lys missense NM_001407925.1:c.1459G>A NP_001394854.1:p.Glu487Lys missense NM_001407926.1:c.1459G>A NP_001394855.1:p.Glu487Lys missense NM_001407927.1:c.1459G>A NP_001394856.1:p.Glu487Lys missense NM_001407928.1:c.1459G>A NP_001394857.1:p.Glu487Lys missense NM_001407929.1:c.1459G>A NP_001394858.1:p.Glu487Lys missense NM_001407930.1:c.1456G>A NP_001394859.1:p.Glu486Lys missense NM_001407931.1:c.1456G>A NP_001394860.1:p.Glu486Lys missense NM_001407932.1:c.1456G>A NP_001394861.1:p.Glu486Lys missense NM_001407933.1:c.1459G>A NP_001394862.1:p.Glu487Lys missense NM_001407934.1:c.1456G>A NP_001394863.1:p.Glu486Lys missense NM_001407935.1:c.1459G>A NP_001394864.1:p.Glu487Lys missense NM_001407936.1:c.1456G>A NP_001394865.1:p.Glu486Lys missense NM_001407937.1:c.1600G>A NP_001394866.1:p.Glu534Lys missense NM_001407938.1:c.1600G>A NP_001394867.1:p.Glu534Lys missense NM_001407939.1:c.1600G>A NP_001394868.1:p.Glu534Lys missense NM_001407940.1:c.1597G>A NP_001394869.1:p.Glu533Lys missense NM_001407941.1:c.1597G>A NP_001394870.1:p.Glu533Lys missense NM_001407942.1:c.1582G>A NP_001394871.1:p.Glu528Lys missense NM_001407943.1:c.1579G>A NP_001394872.1:p.Glu527Lys missense NM_001407944.1:c.1582G>A NP_001394873.1:p.Glu528Lys missense NM_001407945.1:c.1582G>A NP_001394874.1:p.Glu528Lys missense NM_001407946.1:c.1390G>A NP_001394875.1:p.Glu464Lys missense NM_001407947.1:c.1390G>A NP_001394876.1:p.Glu464Lys missense NM_001407948.1:c.1390G>A NP_001394877.1:p.Glu464Lys missense NM_001407949.1:c.1390G>A NP_001394878.1:p.Glu464Lys missense NM_001407950.1:c.1390G>A NP_001394879.1:p.Glu464Lys missense NM_001407951.1:c.1390G>A NP_001394880.1:p.Glu464Lys missense NM_001407952.1:c.1390G>A NP_001394881.1:p.Glu464Lys missense NM_001407953.1:c.1390G>A NP_001394882.1:p.Glu464Lys missense NM_001407954.1:c.1387G>A NP_001394883.1:p.Glu463Lys missense NM_001407955.1:c.1387G>A NP_001394884.1:p.Glu463Lys missense NM_001407956.1:c.1387G>A NP_001394885.1:p.Glu463Lys missense NM_001407957.1:c.1390G>A NP_001394886.1:p.Glu464Lys missense NM_001407958.1:c.1387G>A NP_001394887.1:p.Glu463Lys missense NM_001407959.1:c.1342G>A NP_001394888.1:p.Glu448Lys missense NM_001407960.1:c.1342G>A NP_001394889.1:p.Glu448Lys missense NM_001407962.1:c.1339G>A NP_001394891.1:p.Glu447Lys missense NM_001407963.1:c.1342G>A NP_001394892.1:p.Glu448Lys missense NM_001407964.1:c.1579G>A NP_001394893.1:p.Glu527Lys missense NM_001407965.1:c.1219G>A NP_001394894.1:p.Glu407Lys missense NM_001407966.1:c.835G>A NP_001394895.1:p.Glu279Lys missense NM_001407967.1:c.835G>A NP_001394896.1:p.Glu279Lys missense NM_001407968.1:c.787+936G>A intron variant NM_001407969.1:c.787+936G>A intron variant NM_001407970.1:c.787+936G>A intron variant NM_001407971.1:c.787+936G>A intron variant NM_001407972.1:c.784+936G>A intron variant NM_001407973.1:c.787+936G>A intron variant NM_001407974.1:c.787+936G>A intron variant NM_001407975.1:c.787+936G>A intron variant NM_001407976.1:c.787+936G>A intron variant NM_001407977.1:c.787+936G>A intron variant NM_001407978.1:c.787+936G>A intron variant NM_001407979.1:c.787+936G>A intron variant NM_001407980.1:c.787+936G>A intron variant NM_001407981.1:c.787+936G>A intron variant NM_001407982.1:c.787+936G>A intron variant NM_001407983.1:c.787+936G>A intron variant NM_001407984.1:c.784+936G>A intron variant NM_001407985.1:c.784+936G>A intron variant NM_001407986.1:c.784+936G>A intron variant NM_001407990.1:c.787+936G>A intron variant NM_001407991.1:c.784+936G>A intron variant NM_001407992.1:c.784+936G>A intron variant NM_001407993.1:c.787+936G>A intron variant NM_001408392.1:c.784+936G>A intron variant NM_001408396.1:c.784+936G>A intron variant NM_001408397.1:c.784+936G>A intron variant NM_001408398.1:c.784+936G>A intron variant NM_001408399.1:c.784+936G>A intron variant NM_001408400.1:c.784+936G>A intron variant NM_001408401.1:c.784+936G>A intron variant NM_001408402.1:c.784+936G>A intron variant NM_001408403.1:c.787+936G>A intron variant NM_001408404.1:c.787+936G>A intron variant NM_001408406.1:c.790+933G>A intron variant NM_001408407.1:c.784+936G>A intron variant NM_001408408.1:c.778+936G>A intron variant NM_001408409.1:c.709+936G>A intron variant NM_001408410.1:c.646+936G>A intron variant NM_001408411.1:c.709+936G>A intron variant NM_001408412.1:c.709+936G>A intron variant NM_001408413.1:c.706+936G>A intron variant NM_001408414.1:c.709+936G>A intron variant NM_001408415.1:c.709+936G>A intron variant NM_001408416.1:c.706+936G>A intron variant NM_001408418.1:c.670+2038G>A intron variant NM_001408419.1:c.670+2038G>A intron variant NM_001408420.1:c.670+2038G>A intron variant NM_001408421.1:c.667+2038G>A intron variant NM_001408422.1:c.670+2038G>A intron variant NM_001408423.1:c.670+2038G>A intron variant NM_001408424.1:c.667+2038G>A intron variant NM_001408425.1:c.664+936G>A intron variant NM_001408426.1:c.664+936G>A intron variant NM_001408427.1:c.664+936G>A intron variant NM_001408428.1:c.664+936G>A intron variant NM_001408429.1:c.664+936G>A intron variant NM_001408430.1:c.664+936G>A intron variant NM_001408431.1:c.667+2038G>A intron variant NM_001408432.1:c.661+936G>A intron variant NM_001408433.1:c.661+936G>A intron variant NM_001408434.1:c.661+936G>A intron variant NM_001408435.1:c.661+936G>A intron variant NM_001408436.1:c.664+936G>A intron variant NM_001408437.1:c.664+936G>A intron variant NM_001408438.1:c.664+936G>A intron variant NM_001408439.1:c.664+936G>A intron variant NM_001408440.1:c.664+936G>A intron variant NM_001408441.1:c.664+936G>A intron variant NM_001408442.1:c.664+936G>A intron variant NM_001408443.1:c.664+936G>A intron variant NM_001408444.1:c.664+936G>A intron variant NM_001408445.1:c.661+936G>A intron variant NM_001408446.1:c.661+936G>A intron variant NM_001408447.1:c.661+936G>A intron variant NM_001408448.1:c.661+936G>A intron variant NM_001408450.1:c.661+936G>A intron variant NM_001408451.1:c.652+936G>A intron variant NM_001408452.1:c.646+936G>A intron variant NM_001408453.1:c.646+936G>A intron variant NM_001408454.1:c.646+936G>A intron variant NM_001408455.1:c.646+936G>A intron variant NM_001408456.1:c.646+936G>A intron variant NM_001408457.1:c.646+936G>A intron variant NM_001408458.1:c.646+936G>A intron variant NM_001408459.1:c.646+936G>A intron variant NM_001408460.1:c.646+936G>A intron variant NM_001408461.1:c.646+936G>A intron variant NM_001408462.1:c.643+936G>A intron variant NM_001408463.1:c.643+936G>A intron variant NM_001408464.1:c.643+936G>A intron variant NM_001408465.1:c.643+936G>A intron variant NM_001408466.1:c.646+936G>A intron variant NM_001408467.1:c.646+936G>A intron variant NM_001408468.1:c.643+936G>A intron variant NM_001408469.1:c.646+936G>A intron variant NM_001408470.1:c.643+936G>A intron variant NM_001408472.1:c.787+936G>A intron variant NM_001408473.1:c.784+936G>A intron variant NM_001408474.1:c.586+936G>A intron variant NM_001408475.1:c.583+936G>A intron variant NM_001408476.1:c.586+936G>A intron variant NM_001408478.1:c.577+936G>A intron variant NM_001408479.1:c.577+936G>A intron variant NM_001408480.1:c.577+936G>A intron variant NM_001408481.1:c.577+936G>A intron variant NM_001408482.1:c.577+936G>A intron variant NM_001408483.1:c.577+936G>A intron variant NM_001408484.1:c.577+936G>A intron variant NM_001408485.1:c.577+936G>A intron variant NM_001408489.1:c.577+936G>A intron variant NM_001408490.1:c.574+936G>A intron variant NM_001408491.1:c.574+936G>A intron variant NM_001408492.1:c.577+936G>A intron variant NM_001408493.1:c.574+936G>A intron variant NM_001408494.1:c.548-2776G>A intron variant NM_001408495.1:c.545-2776G>A intron variant NM_001408496.1:c.523+936G>A intron variant NM_001408497.1:c.523+936G>A intron variant NM_001408498.1:c.523+936G>A intron variant NM_001408499.1:c.523+936G>A intron variant NM_001408500.1:c.523+936G>A intron variant NM_001408501.1:c.523+936G>A intron variant NM_001408502.1:c.454+936G>A intron variant NM_001408503.1:c.520+936G>A intron variant NM_001408504.1:c.520+936G>A intron variant NM_001408505.1:c.520+936G>A intron variant NM_001408506.1:c.460+2038G>A intron variant NM_001408507.1:c.460+2038G>A intron variant NM_001408508.1:c.451+936G>A intron variant NM_001408509.1:c.451+936G>A intron variant NM_001408510.1:c.406+936G>A intron variant NM_001408511.1:c.404-2776G>A intron variant NM_001408512.1:c.283+936G>A intron variant NM_001408513.1:c.577+936G>A intron variant NM_001408514.1:c.577+936G>A intron variant NM_007297.4:c.1582G>A NP_009228.2:p.Glu528Lys missense NM_007298.4:c.787+936G>A intron variant NM_007299.4:c.787+936G>A intron variant NM_007300.3:c.1723G>A NM_007300.4:c.1723G>A NP_009231.2:p.Glu575Lys missense NR_027676.1:n.1859G>A NC_000017.11:g.43093808C>T NC_000017.10:g.41245825C>T NG_005905.2:g.124176G>A LRG_292:g.124176G>A LRG_292t1:c.1723G>A LRG_292p1:p.Glu575Lys - Protein change
- E575K, E528K, E447K, E507K, E533K, E549K, E448K, E463K, E464K, E504K, E534K, E548K, E407K, E486K, E487K, E505K, E508K, E572K, E279K, E527K, E574K
- Other names
- p.E575K:GAA>AAA
- Canonical SPDI
- NC_000017.11:43093807:C:T
-
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.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
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. |
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BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
12998 | 14798 |
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. |
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Likely benign (1) |
criteria provided, single submitter
|
Nov 10, 2023 | RCV000167785.9 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Aug 22, 2023 | RCV000166298.17 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Aug 24, 2023 | RCV000656786.4 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
|
May 16, 2023 | RCV000662632.6 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Oct 28, 2021 | RCV002483062.1 |
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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Uncertain significance
(Dec 03, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210110.12
First in ClinVar: Feb 24, 2015 Last updated: Jul 09, 2018 |
Comment:
Observed in individuals with a personal and/or family history of breast and/or ovarian cancer; however, did not co-segregate with breast cancer in one family (Coupier … (more)
Observed in individuals with a personal and/or family history of breast and/or ovarian cancer; however, did not co-segregate with breast cancer in one family (Coupier 2004, Suter 2004, Anczukow 2008); Published functional studies demonstrate a damaging effect: impaired DNA break repair activity (Coupier 2004); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Also known as 1842G>A; This variant is associated with the following publications: (PMID: 25348012, 14647443, 20858050, 14973102, 23893897, 26269718, 18273839, 31825140) (less)
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Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003851082.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
|
Likely benign
(Nov 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000075582.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
|
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Uncertain significance
(Jul 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000785316.2
First in ClinVar: Jul 15, 2018 Last updated: Jul 15, 2018 |
|
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Uncertain significance
(Oct 28, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
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
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002787638.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
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Uncertain significance
(Aug 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600264.3
First in ClinVar: Sep 28, 2017 Last updated: Jan 06, 2024 |
Comment:
In the published literature, the variant has been reported in high-risk breast and/or ovarian cancer families (PMIDs: 34981296 (2022), 31954625 (2020), 31825140 (2019), 27062684 (2016), … (more)
In the published literature, the variant has been reported in high-risk breast and/or ovarian cancer families (PMIDs: 34981296 (2022), 31954625 (2020), 31825140 (2019), 27062684 (2016), 18273839 (2008), 14647443 (2004), 14973102 (2004)), as well as in an individual with breast cancer in a large scale breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA1)). This variant was also reported to be damaging to DNA break repair activity in a cell-based study (PMID: 14647443 (2004)). The frequency of this variant in the general population, 0.00002 (5/250624 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Uncertain significance
(May 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001354713.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces glutamic acid with lysine at codon 575 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces glutamic acid with lysine at codon 575 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). One functional study observed partial activity in an ex vivo repair assay of an extrachromosomal plasmid (PMID: 14647443). This variant has been reported in at least two unrelated individuals affected with breast cancer (PMID: 14647443, 14973102) and two suspected hereditary breast and ovarian cancer families (PMID: 27062684, 31954625). However, this variant did not segregate completely with breast cancer affected members of a family (PMID: 14647443). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_000164). This variant has been identified in 5/250624 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
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Uncertain Significance
(May 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004818293.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This missense variant replaces glutamic acid with lysine at codon 575 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces glutamic acid with lysine at codon 575 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). One functional study observed partial activity in an ex vivo repair assay of an extrachromosomal plasmid (PMID: 14647443). This variant has been reported in at least two unrelated individuals affected with breast cancer (PMID: 14647443, 14973102) and two suspected hereditary breast and ovarian cancer families (PMID: 27062684, 31954625). However, this variant did not segregate completely with breast cancer affected members of a family (PMID: 14647443). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_000164). This variant has been identified in 5/250624 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 2
|
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Uncertain significance
(Aug 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000217082.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.E575K variant (also known as c.1723G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.E575K variant (also known as c.1723G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1723. The glutamic acid at codon 575 is replaced by lysine, an amino acid with similar properties. In one study, lymphoblast cell lines with this alteration demonstrated impaired fidelity of double strand breakage repair by DNA end-joining compared to the normal control cell line. However, the alteration did not segregate with disease in one family (Coupier I et al. Oncogene 2004 Jan; 23(4):914-9). In another study, this variant was shown to have no effect on alternate splicing using minigene splicing assay (Anczukow O et al. Genes Chromosomes Cancer. 2008; 47:418-26). An additional paper reported this alteration in 1/645 women with breast cancer from Shanghai, China (Suter NM et al, Cancer Epidemiol. Biomarkers Prev. 2004 Feb; 13(2):181-9), and in a study of 1854 high-risk breast/ovarian cancer families in Italy, this alteration was detected in 1 family (Azzollini J et al. Eur J Intern Med, 2016 Jul;32:65-71). Of note, this alteration is also designated as 1842G>A in published literature. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(May 05, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV003927162.1
First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023 |
Comment:
a variant of uncertain significance was detected in the BRCA1 gene. The p.E575K variant (also known as c.1723G>A), located in coding region of the BRCA1 … (more)
a variant of uncertain significance was detected in the BRCA1 gene. The p.E575K variant (also known as c.1723G>A), located in coding region of the BRCA1 gene, results from a G to A substitution at nucleotide position 1723. The glutamic acid at codon 575 is replaced by lysine, an amino acid with similar properties. The alteration did not segregate with disease in one family (PMID 14647443). In another study, this variant was shown to have no effect on alternate splicing using minigene splicing assay (PMID 18273839). An additional paper reported this alteration in 1/645 women with breast cancer from Shanghai, China (PMID 14973102). Of note, this alteration is also designated as 1842G>A in published literature. This amino acid position is not well conserved in available vertebrate species. ClinVar has an entry for this variant with 6 submissions all of which classify it as of uncertain significance, 2 stars, no conflicts. In-silico prediction for this alteration shows Pathogenic computational verdict based on 8 pathogenic predictions from BayesDel_addAF, DANN, DEOGEN2, LIST-S2, M-CAP, MVP, MutationAssessor and SIFT vs 4 benign predictions from EIGEN, FATHMM-MKL, MutationTaster and PrimateAI. Therefore, this variant is classified as on uncertain significance. Pathogenic/Likely pathogenic BRCA1 variants cause hereditary breast/ovarian cancer syndrome (HBOC). (less)
Sex: female
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Uncertain significance
(Mar 02, 2020)
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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: SCV004244116.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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BRCA1 Norway: comparison of classification for BRCA1 germline variants detected in families with suspected hereditary breast and ovarian cancer between different laboratories. | Hovland HN | Familial cancer | 2022 | PMID: 34981296 |
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 |
BRCA1-BRCA2 mutation analysis results in 910 individuals: Mutation distribution and 8 novel mutations. | Solmaz AE | Cancer genetics | 2020 | PMID: 31954625 |
Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients. | Gao X | Human mutation | 2020 | PMID: 31825140 |
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 |
Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations. | Martelotto LG | Genome biology | 2014 | PMID: 25348012 |
A one-step prescreening for point mutations and large rearrangement in BRCA1 and BRCA2 genes using quantitative polymerase chain reaction and high-resolution melting curve analysis. | Coulet F | Genetic testing and molecular biomarkers | 2010 | PMID: 20858050 |
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 |
Unclassified variants identified in BRCA1 exon 11: Consequences on splicing. | Anczuków O | Genes, chromosomes & cancer | 2008 | PMID: 18273839 |
BRCA1 and BRCA2 mutations in women from Shanghai China. | Suter NM | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2004 | PMID: 14973102 |
Fidelity of DNA double-strand break repair in heterozygous cell lines harbouring BRCA1 missense mutations. | Coupier I | Oncogene | 2004 | PMID: 14647443 |
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Text-mined citations for rs397508902 ...
HelpRecord last updated Aug 18, 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.