Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1912G>A (p.Glu638Lys)
Germline
Classification
Help
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.
(9)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(2); Benign(1); Likely benign(2)
Uncertain significance(2); Benign(1); Likely benign(2)
9
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.1912G>A (p.Glu638Lys)
Variation ID: 37433 Accession: VCV000037433.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093619 (GRCh38) [ NCBI UCSC ] 17: 41245636 (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 Apr 1, 2014 May 1, 2024 Nov 17, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.1912G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu638Lys missense NM_001407571.1:c.1699G>A NP_001394500.1:p.Glu567Lys missense NM_001407581.1:c.1912G>A NP_001394510.1:p.Glu638Lys missense NM_001407582.1:c.1912G>A NP_001394511.1:p.Glu638Lys missense NM_001407583.1:c.1912G>A NP_001394512.1:p.Glu638Lys missense NM_001407585.1:c.1912G>A NP_001394514.1:p.Glu638Lys missense NM_001407587.1:c.1909G>A NP_001394516.1:p.Glu637Lys missense NM_001407590.1:c.1909G>A NP_001394519.1:p.Glu637Lys missense NM_001407591.1:c.1909G>A NP_001394520.1:p.Glu637Lys missense NM_001407593.1:c.1912G>A NP_001394522.1:p.Glu638Lys missense NM_001407594.1:c.1912G>A NP_001394523.1:p.Glu638Lys missense NM_001407596.1:c.1912G>A NP_001394525.1:p.Glu638Lys missense NM_001407597.1:c.1912G>A NP_001394526.1:p.Glu638Lys missense NM_001407598.1:c.1912G>A NP_001394527.1:p.Glu638Lys missense NM_001407602.1:c.1912G>A NP_001394531.1:p.Glu638Lys missense NM_001407603.1:c.1912G>A NP_001394532.1:p.Glu638Lys missense NM_001407605.1:c.1912G>A NP_001394534.1:p.Glu638Lys missense NM_001407610.1:c.1909G>A NP_001394539.1:p.Glu637Lys missense NM_001407611.1:c.1909G>A NP_001394540.1:p.Glu637Lys missense NM_001407612.1:c.1909G>A NP_001394541.1:p.Glu637Lys missense NM_001407613.1:c.1909G>A NP_001394542.1:p.Glu637Lys missense NM_001407614.1:c.1909G>A NP_001394543.1:p.Glu637Lys missense NM_001407615.1:c.1909G>A NP_001394544.1:p.Glu637Lys missense NM_001407616.1:c.1912G>A NP_001394545.1:p.Glu638Lys missense NM_001407617.1:c.1912G>A NP_001394546.1:p.Glu638Lys missense NM_001407618.1:c.1912G>A NP_001394547.1:p.Glu638Lys missense NM_001407619.1:c.1912G>A NP_001394548.1:p.Glu638Lys missense NM_001407620.1:c.1912G>A NP_001394549.1:p.Glu638Lys missense NM_001407621.1:c.1912G>A NP_001394550.1:p.Glu638Lys missense NM_001407622.1:c.1912G>A NP_001394551.1:p.Glu638Lys missense NM_001407623.1:c.1912G>A NP_001394552.1:p.Glu638Lys missense NM_001407624.1:c.1912G>A NP_001394553.1:p.Glu638Lys missense NM_001407625.1:c.1912G>A NP_001394554.1:p.Glu638Lys missense NM_001407626.1:c.1912G>A NP_001394555.1:p.Glu638Lys missense NM_001407627.1:c.1909G>A NP_001394556.1:p.Glu637Lys missense NM_001407628.1:c.1909G>A NP_001394557.1:p.Glu637Lys missense NM_001407629.1:c.1909G>A NP_001394558.1:p.Glu637Lys missense NM_001407630.1:c.1909G>A NP_001394559.1:p.Glu637Lys missense NM_001407631.1:c.1909G>A NP_001394560.1:p.Glu637Lys missense NM_001407632.1:c.1909G>A NP_001394561.1:p.Glu637Lys missense NM_001407633.1:c.1909G>A NP_001394562.1:p.Glu637Lys missense NM_001407634.1:c.1909G>A NP_001394563.1:p.Glu637Lys missense NM_001407635.1:c.1909G>A NP_001394564.1:p.Glu637Lys missense NM_001407636.1:c.1909G>A NP_001394565.1:p.Glu637Lys missense NM_001407637.1:c.1909G>A NP_001394566.1:p.Glu637Lys missense NM_001407638.1:c.1909G>A NP_001394567.1:p.Glu637Lys missense NM_001407639.1:c.1912G>A NP_001394568.1:p.Glu638Lys missense NM_001407640.1:c.1912G>A NP_001394569.1:p.Glu638Lys missense NM_001407641.1:c.1912G>A NP_001394570.1:p.Glu638Lys missense NM_001407642.1:c.1912G>A NP_001394571.1:p.Glu638Lys missense NM_001407644.1:c.1909G>A NP_001394573.1:p.Glu637Lys missense NM_001407645.1:c.1909G>A NP_001394574.1:p.Glu637Lys missense NM_001407646.1:c.1903G>A NP_001394575.1:p.Glu635Lys missense NM_001407647.1:c.1903G>A NP_001394576.1:p.Glu635Lys missense NM_001407648.1:c.1789G>A NP_001394577.1:p.Glu597Lys missense NM_001407649.1:c.1786G>A NP_001394578.1:p.Glu596Lys missense NM_001407652.1:c.1912G>A NP_001394581.1:p.Glu638Lys missense NM_001407653.1:c.1834G>A NP_001394582.1:p.Glu612Lys missense NM_001407654.1:c.1834G>A NP_001394583.1:p.Glu612Lys missense NM_001407655.1:c.1834G>A NP_001394584.1:p.Glu612Lys missense NM_001407656.1:c.1834G>A NP_001394585.1:p.Glu612Lys missense NM_001407657.1:c.1834G>A NP_001394586.1:p.Glu612Lys missense NM_001407658.1:c.1834G>A NP_001394587.1:p.Glu612Lys missense NM_001407659.1:c.1831G>A NP_001394588.1:p.Glu611Lys missense NM_001407660.1:c.1831G>A NP_001394589.1:p.Glu611Lys missense NM_001407661.1:c.1831G>A NP_001394590.1:p.Glu611Lys missense NM_001407662.1:c.1831G>A NP_001394591.1:p.Glu611Lys missense NM_001407663.1:c.1834G>A NP_001394592.1:p.Glu612Lys missense NM_001407664.1:c.1789G>A NP_001394593.1:p.Glu597Lys missense NM_001407665.1:c.1789G>A NP_001394594.1:p.Glu597Lys missense NM_001407666.1:c.1789G>A NP_001394595.1:p.Glu597Lys missense NM_001407667.1:c.1789G>A NP_001394596.1:p.Glu597Lys missense NM_001407668.1:c.1789G>A NP_001394597.1:p.Glu597Lys missense NM_001407669.1:c.1789G>A NP_001394598.1:p.Glu597Lys missense NM_001407670.1:c.1786G>A NP_001394599.1:p.Glu596Lys missense NM_001407671.1:c.1786G>A NP_001394600.1:p.Glu596Lys missense NM_001407672.1:c.1786G>A NP_001394601.1:p.Glu596Lys missense NM_001407673.1:c.1786G>A NP_001394602.1:p.Glu596Lys missense NM_001407674.1:c.1789G>A NP_001394603.1:p.Glu597Lys missense NM_001407675.1:c.1789G>A NP_001394604.1:p.Glu597Lys missense NM_001407676.1:c.1789G>A NP_001394605.1:p.Glu597Lys missense NM_001407677.1:c.1789G>A NP_001394606.1:p.Glu597Lys missense NM_001407678.1:c.1789G>A NP_001394607.1:p.Glu597Lys missense NM_001407679.1:c.1789G>A NP_001394608.1:p.Glu597Lys missense NM_001407680.1:c.1789G>A NP_001394609.1:p.Glu597Lys missense NM_001407681.1:c.1789G>A NP_001394610.1:p.Glu597Lys missense NM_001407682.1:c.1789G>A NP_001394611.1:p.Glu597Lys missense NM_001407683.1:c.1789G>A NP_001394612.1:p.Glu597Lys missense NM_001407684.1:c.1912G>A NP_001394613.1:p.Glu638Lys missense NM_001407685.1:c.1786G>A NP_001394614.1:p.Glu596Lys missense NM_001407686.1:c.1786G>A NP_001394615.1:p.Glu596Lys missense NM_001407687.1:c.1786G>A NP_001394616.1:p.Glu596Lys missense NM_001407688.1:c.1786G>A NP_001394617.1:p.Glu596Lys missense NM_001407689.1:c.1786G>A NP_001394618.1:p.Glu596Lys missense NM_001407690.1:c.1786G>A NP_001394619.1:p.Glu596Lys missense NM_001407691.1:c.1786G>A NP_001394620.1:p.Glu596Lys missense NM_001407692.1:c.1771G>A NP_001394621.1:p.Glu591Lys missense NM_001407694.1:c.1771G>A NP_001394623.1:p.Glu591Lys missense NM_001407695.1:c.1771G>A NP_001394624.1:p.Glu591Lys missense NM_001407696.1:c.1771G>A NP_001394625.1:p.Glu591Lys missense NM_001407697.1:c.1771G>A NP_001394626.1:p.Glu591Lys missense NM_001407698.1:c.1771G>A NP_001394627.1:p.Glu591Lys missense NM_001407724.1:c.1771G>A NP_001394653.1:p.Glu591Lys missense NM_001407725.1:c.1771G>A NP_001394654.1:p.Glu591Lys missense NM_001407726.1:c.1771G>A NP_001394655.1:p.Glu591Lys missense NM_001407727.1:c.1771G>A NP_001394656.1:p.Glu591Lys missense NM_001407728.1:c.1771G>A NP_001394657.1:p.Glu591Lys missense NM_001407729.1:c.1771G>A NP_001394658.1:p.Glu591Lys missense NM_001407730.1:c.1771G>A NP_001394659.1:p.Glu591Lys missense NM_001407731.1:c.1771G>A NP_001394660.1:p.Glu591Lys missense NM_001407732.1:c.1771G>A NP_001394661.1:p.Glu591Lys missense NM_001407733.1:c.1771G>A NP_001394662.1:p.Glu591Lys missense NM_001407734.1:c.1771G>A NP_001394663.1:p.Glu591Lys missense NM_001407735.1:c.1771G>A NP_001394664.1:p.Glu591Lys missense NM_001407736.1:c.1771G>A NP_001394665.1:p.Glu591Lys missense NM_001407737.1:c.1771G>A NP_001394666.1:p.Glu591Lys missense NM_001407738.1:c.1771G>A NP_001394667.1:p.Glu591Lys missense NM_001407739.1:c.1771G>A NP_001394668.1:p.Glu591Lys missense NM_001407740.1:c.1768G>A NP_001394669.1:p.Glu590Lys missense NM_001407741.1:c.1768G>A NP_001394670.1:p.Glu590Lys missense NM_001407742.1:c.1768G>A NP_001394671.1:p.Glu590Lys missense NM_001407743.1:c.1768G>A NP_001394672.1:p.Glu590Lys missense NM_001407744.1:c.1768G>A NP_001394673.1:p.Glu590Lys missense NM_001407745.1:c.1768G>A NP_001394674.1:p.Glu590Lys missense NM_001407746.1:c.1768G>A NP_001394675.1:p.Glu590Lys missense NM_001407747.1:c.1768G>A NP_001394676.1:p.Glu590Lys missense NM_001407748.1:c.1768G>A NP_001394677.1:p.Glu590Lys missense NM_001407749.1:c.1768G>A NP_001394678.1:p.Glu590Lys missense NM_001407750.1:c.1771G>A NP_001394679.1:p.Glu591Lys missense NM_001407751.1:c.1771G>A NP_001394680.1:p.Glu591Lys missense NM_001407752.1:c.1771G>A NP_001394681.1:p.Glu591Lys missense NM_001407838.1:c.1768G>A NP_001394767.1:p.Glu590Lys missense NM_001407839.1:c.1768G>A NP_001394768.1:p.Glu590Lys missense NM_001407841.1:c.1768G>A NP_001394770.1:p.Glu590Lys missense NM_001407842.1:c.1768G>A NP_001394771.1:p.Glu590Lys missense NM_001407843.1:c.1768G>A NP_001394772.1:p.Glu590Lys missense NM_001407844.1:c.1768G>A NP_001394773.1:p.Glu590Lys missense NM_001407845.1:c.1768G>A NP_001394774.1:p.Glu590Lys missense NM_001407846.1:c.1768G>A NP_001394775.1:p.Glu590Lys missense NM_001407847.1:c.1768G>A NP_001394776.1:p.Glu590Lys missense NM_001407848.1:c.1768G>A NP_001394777.1:p.Glu590Lys missense NM_001407849.1:c.1768G>A NP_001394778.1:p.Glu590Lys missense NM_001407850.1:c.1771G>A NP_001394779.1:p.Glu591Lys missense NM_001407851.1:c.1771G>A NP_001394780.1:p.Glu591Lys missense NM_001407852.1:c.1771G>A NP_001394781.1:p.Glu591Lys missense NM_001407853.1:c.1699G>A NP_001394782.1:p.Glu567Lys missense NM_001407854.1:c.1912G>A NP_001394783.1:p.Glu638Lys missense NM_001407858.1:c.1912G>A NP_001394787.1:p.Glu638Lys missense NM_001407859.1:c.1912G>A NP_001394788.1:p.Glu638Lys missense NM_001407860.1:c.1909G>A NP_001394789.1:p.Glu637Lys missense NM_001407861.1:c.1909G>A NP_001394790.1:p.Glu637Lys missense NM_001407862.1:c.1711G>A NP_001394791.1:p.Glu571Lys missense NM_001407863.1:c.1789G>A NP_001394792.1:p.Glu597Lys missense NM_001407874.1:c.1708G>A NP_001394803.1:p.Glu570Lys missense NM_001407875.1:c.1708G>A NP_001394804.1:p.Glu570Lys missense NM_001407879.1:c.1702G>A NP_001394808.1:p.Glu568Lys missense NM_001407881.1:c.1702G>A NP_001394810.1:p.Glu568Lys missense NM_001407882.1:c.1702G>A NP_001394811.1:p.Glu568Lys missense NM_001407884.1:c.1702G>A NP_001394813.1:p.Glu568Lys missense NM_001407885.1:c.1702G>A NP_001394814.1:p.Glu568Lys missense NM_001407886.1:c.1702G>A NP_001394815.1:p.Glu568Lys missense NM_001407887.1:c.1702G>A NP_001394816.1:p.Glu568Lys missense NM_001407889.1:c.1702G>A NP_001394818.1:p.Glu568Lys missense NM_001407894.1:c.1699G>A NP_001394823.1:p.Glu567Lys missense NM_001407895.1:c.1699G>A NP_001394824.1:p.Glu567Lys missense NM_001407896.1:c.1699G>A NP_001394825.1:p.Glu567Lys missense NM_001407897.1:c.1699G>A NP_001394826.1:p.Glu567Lys missense NM_001407898.1:c.1699G>A NP_001394827.1:p.Glu567Lys missense NM_001407899.1:c.1699G>A NP_001394828.1:p.Glu567Lys missense NM_001407900.1:c.1702G>A NP_001394829.1:p.Glu568Lys missense NM_001407902.1:c.1702G>A NP_001394831.1:p.Glu568Lys missense NM_001407904.1:c.1702G>A NP_001394833.1:p.Glu568Lys missense NM_001407906.1:c.1702G>A NP_001394835.1:p.Glu568Lys missense NM_001407907.1:c.1702G>A NP_001394836.1:p.Glu568Lys missense NM_001407908.1:c.1702G>A NP_001394837.1:p.Glu568Lys missense NM_001407909.1:c.1702G>A NP_001394838.1:p.Glu568Lys missense NM_001407910.1:c.1702G>A NP_001394839.1:p.Glu568Lys missense NM_001407915.1:c.1699G>A NP_001394844.1:p.Glu567Lys missense NM_001407916.1:c.1699G>A NP_001394845.1:p.Glu567Lys missense NM_001407917.1:c.1699G>A NP_001394846.1:p.Glu567Lys missense NM_001407918.1:c.1699G>A NP_001394847.1:p.Glu567Lys missense NM_001407919.1:c.1789G>A NP_001394848.1:p.Glu597Lys missense NM_001407920.1:c.1648G>A NP_001394849.1:p.Glu550Lys missense NM_001407921.1:c.1648G>A NP_001394850.1:p.Glu550Lys missense NM_001407922.1:c.1648G>A NP_001394851.1:p.Glu550Lys missense NM_001407923.1:c.1648G>A NP_001394852.1:p.Glu550Lys missense NM_001407924.1:c.1648G>A NP_001394853.1:p.Glu550Lys missense NM_001407925.1:c.1648G>A NP_001394854.1:p.Glu550Lys missense NM_001407926.1:c.1648G>A NP_001394855.1:p.Glu550Lys missense NM_001407927.1:c.1648G>A NP_001394856.1:p.Glu550Lys missense NM_001407928.1:c.1648G>A NP_001394857.1:p.Glu550Lys missense NM_001407929.1:c.1648G>A NP_001394858.1:p.Glu550Lys missense NM_001407930.1:c.1645G>A NP_001394859.1:p.Glu549Lys missense NM_001407931.1:c.1645G>A NP_001394860.1:p.Glu549Lys missense NM_001407932.1:c.1645G>A NP_001394861.1:p.Glu549Lys missense NM_001407933.1:c.1648G>A NP_001394862.1:p.Glu550Lys missense NM_001407934.1:c.1645G>A NP_001394863.1:p.Glu549Lys missense NM_001407935.1:c.1648G>A NP_001394864.1:p.Glu550Lys missense NM_001407936.1:c.1645G>A NP_001394865.1:p.Glu549Lys missense NM_001407937.1:c.1789G>A NP_001394866.1:p.Glu597Lys missense NM_001407938.1:c.1789G>A NP_001394867.1:p.Glu597Lys missense NM_001407939.1:c.1789G>A NP_001394868.1:p.Glu597Lys missense NM_001407940.1:c.1786G>A NP_001394869.1:p.Glu596Lys missense NM_001407941.1:c.1786G>A NP_001394870.1:p.Glu596Lys missense NM_001407942.1:c.1771G>A NP_001394871.1:p.Glu591Lys missense NM_001407943.1:c.1768G>A NP_001394872.1:p.Glu590Lys missense NM_001407944.1:c.1771G>A NP_001394873.1:p.Glu591Lys missense NM_001407945.1:c.1771G>A NP_001394874.1:p.Glu591Lys missense NM_001407946.1:c.1579G>A NP_001394875.1:p.Glu527Lys missense NM_001407947.1:c.1579G>A NP_001394876.1:p.Glu527Lys missense NM_001407948.1:c.1579G>A NP_001394877.1:p.Glu527Lys missense NM_001407949.1:c.1579G>A NP_001394878.1:p.Glu527Lys missense NM_001407950.1:c.1579G>A NP_001394879.1:p.Glu527Lys missense NM_001407951.1:c.1579G>A NP_001394880.1:p.Glu527Lys missense NM_001407952.1:c.1579G>A NP_001394881.1:p.Glu527Lys missense NM_001407953.1:c.1579G>A NP_001394882.1:p.Glu527Lys missense NM_001407954.1:c.1576G>A NP_001394883.1:p.Glu526Lys missense NM_001407955.1:c.1576G>A NP_001394884.1:p.Glu526Lys missense NM_001407956.1:c.1576G>A NP_001394885.1:p.Glu526Lys missense NM_001407957.1:c.1579G>A NP_001394886.1:p.Glu527Lys missense NM_001407958.1:c.1576G>A NP_001394887.1:p.Glu526Lys missense NM_001407959.1:c.1531G>A NP_001394888.1:p.Glu511Lys missense NM_001407960.1:c.1531G>A NP_001394889.1:p.Glu511Lys missense NM_001407962.1:c.1528G>A NP_001394891.1:p.Glu510Lys missense NM_001407963.1:c.1531G>A NP_001394892.1:p.Glu511Lys missense NM_001407964.1:c.1768G>A NP_001394893.1:p.Glu590Lys missense NM_001407965.1:c.1408G>A NP_001394894.1:p.Glu470Lys missense NM_001407966.1:c.1024G>A NP_001394895.1:p.Glu342Lys missense NM_001407967.1:c.1024G>A NP_001394896.1:p.Glu342Lys missense NM_001407968.1:c.787+1125G>A intron variant NM_001407969.1:c.787+1125G>A intron variant NM_001407970.1:c.787+1125G>A intron variant NM_001407971.1:c.787+1125G>A intron variant NM_001407972.1:c.784+1125G>A intron variant NM_001407973.1:c.787+1125G>A intron variant NM_001407974.1:c.787+1125G>A intron variant NM_001407975.1:c.787+1125G>A intron variant NM_001407976.1:c.787+1125G>A intron variant NM_001407977.1:c.787+1125G>A intron variant NM_001407978.1:c.787+1125G>A intron variant NM_001407979.1:c.787+1125G>A intron variant NM_001407980.1:c.787+1125G>A intron variant NM_001407981.1:c.787+1125G>A intron variant NM_001407982.1:c.787+1125G>A intron variant NM_001407983.1:c.787+1125G>A intron variant NM_001407984.1:c.784+1125G>A intron variant NM_001407985.1:c.784+1125G>A intron variant NM_001407986.1:c.784+1125G>A intron variant NM_001407990.1:c.787+1125G>A intron variant NM_001407991.1:c.784+1125G>A intron variant NM_001407992.1:c.784+1125G>A intron variant NM_001407993.1:c.787+1125G>A intron variant NM_001408392.1:c.784+1125G>A intron variant NM_001408396.1:c.784+1125G>A intron variant NM_001408397.1:c.784+1125G>A intron variant NM_001408398.1:c.784+1125G>A intron variant NM_001408399.1:c.784+1125G>A intron variant NM_001408400.1:c.784+1125G>A intron variant NM_001408401.1:c.784+1125G>A intron variant NM_001408402.1:c.784+1125G>A intron variant NM_001408403.1:c.787+1125G>A intron variant NM_001408404.1:c.787+1125G>A intron variant NM_001408406.1:c.790+1122G>A intron variant NM_001408407.1:c.784+1125G>A intron variant NM_001408408.1:c.778+1125G>A intron variant NM_001408409.1:c.709+1125G>A intron variant NM_001408410.1:c.646+1125G>A intron variant NM_001408411.1:c.709+1125G>A intron variant NM_001408412.1:c.709+1125G>A intron variant NM_001408413.1:c.706+1125G>A intron variant NM_001408414.1:c.709+1125G>A intron variant NM_001408415.1:c.709+1125G>A intron variant NM_001408416.1:c.706+1125G>A intron variant NM_001408418.1:c.670+2227G>A intron variant NM_001408419.1:c.670+2227G>A intron variant NM_001408420.1:c.670+2227G>A intron variant NM_001408421.1:c.667+2227G>A intron variant NM_001408422.1:c.670+2227G>A intron variant NM_001408423.1:c.670+2227G>A intron variant NM_001408424.1:c.667+2227G>A intron variant NM_001408425.1:c.664+1125G>A intron variant NM_001408426.1:c.664+1125G>A intron variant NM_001408427.1:c.664+1125G>A intron variant NM_001408428.1:c.664+1125G>A intron variant NM_001408429.1:c.664+1125G>A intron variant NM_001408430.1:c.664+1125G>A intron variant NM_001408431.1:c.667+2227G>A intron variant NM_001408432.1:c.661+1125G>A intron variant NM_001408433.1:c.661+1125G>A intron variant NM_001408434.1:c.661+1125G>A intron variant NM_001408435.1:c.661+1125G>A intron variant NM_001408436.1:c.664+1125G>A intron variant NM_001408437.1:c.664+1125G>A intron variant NM_001408438.1:c.664+1125G>A intron variant NM_001408439.1:c.664+1125G>A intron variant NM_001408440.1:c.664+1125G>A intron variant NM_001408441.1:c.664+1125G>A intron variant NM_001408442.1:c.664+1125G>A intron variant NM_001408443.1:c.664+1125G>A intron variant NM_001408444.1:c.664+1125G>A intron variant NM_001408445.1:c.661+1125G>A intron variant NM_001408446.1:c.661+1125G>A intron variant NM_001408447.1:c.661+1125G>A intron variant NM_001408448.1:c.661+1125G>A intron variant NM_001408450.1:c.661+1125G>A intron variant NM_001408451.1:c.652+1125G>A intron variant NM_001408452.1:c.646+1125G>A intron variant NM_001408453.1:c.646+1125G>A intron variant NM_001408454.1:c.646+1125G>A intron variant NM_001408455.1:c.646+1125G>A intron variant NM_001408456.1:c.646+1125G>A intron variant NM_001408457.1:c.646+1125G>A intron variant NM_001408458.1:c.646+1125G>A intron variant NM_001408459.1:c.646+1125G>A intron variant NM_001408460.1:c.646+1125G>A intron variant NM_001408461.1:c.646+1125G>A intron variant NM_001408462.1:c.643+1125G>A intron variant NM_001408463.1:c.643+1125G>A intron variant NM_001408464.1:c.643+1125G>A intron variant NM_001408465.1:c.643+1125G>A intron variant NM_001408466.1:c.646+1125G>A intron variant NM_001408467.1:c.646+1125G>A intron variant NM_001408468.1:c.643+1125G>A intron variant NM_001408469.1:c.646+1125G>A intron variant NM_001408470.1:c.643+1125G>A intron variant NM_001408472.1:c.787+1125G>A intron variant NM_001408473.1:c.784+1125G>A intron variant NM_001408474.1:c.586+1125G>A intron variant NM_001408475.1:c.583+1125G>A intron variant NM_001408476.1:c.586+1125G>A intron variant NM_001408478.1:c.577+1125G>A intron variant NM_001408479.1:c.577+1125G>A intron variant NM_001408480.1:c.577+1125G>A intron variant NM_001408481.1:c.577+1125G>A intron variant NM_001408482.1:c.577+1125G>A intron variant NM_001408483.1:c.577+1125G>A intron variant NM_001408484.1:c.577+1125G>A intron variant NM_001408485.1:c.577+1125G>A intron variant NM_001408489.1:c.577+1125G>A intron variant NM_001408490.1:c.574+1125G>A intron variant NM_001408491.1:c.574+1125G>A intron variant NM_001408492.1:c.577+1125G>A intron variant NM_001408493.1:c.574+1125G>A intron variant NM_001408494.1:c.548-2587G>A intron variant NM_001408495.1:c.545-2587G>A intron variant NM_001408496.1:c.523+1125G>A intron variant NM_001408497.1:c.523+1125G>A intron variant NM_001408498.1:c.523+1125G>A intron variant NM_001408499.1:c.523+1125G>A intron variant NM_001408500.1:c.523+1125G>A intron variant NM_001408501.1:c.523+1125G>A intron variant NM_001408502.1:c.454+1125G>A intron variant NM_001408503.1:c.520+1125G>A intron variant NM_001408504.1:c.520+1125G>A intron variant NM_001408505.1:c.520+1125G>A intron variant NM_001408506.1:c.460+2227G>A intron variant NM_001408507.1:c.460+2227G>A intron variant NM_001408508.1:c.451+1125G>A intron variant NM_001408509.1:c.451+1125G>A intron variant NM_001408510.1:c.406+1125G>A intron variant NM_001408511.1:c.404-2587G>A intron variant NM_001408512.1:c.283+1125G>A intron variant NM_001408513.1:c.577+1125G>A intron variant NM_001408514.1:c.577+1125G>A intron variant NM_007297.4:c.1771G>A NP_009228.2:p.Glu591Lys missense NM_007298.4:c.787+1125G>A intron variant NM_007299.4:c.787+1125G>A intron variant NM_007300.4:c.1912G>A NP_009231.2:p.Glu638Lys missense NR_027676.1:n.2048G>A NC_000017.11:g.43093619C>T NC_000017.10:g.41245636C>T NG_005905.2:g.124365G>A LRG_292:g.124365G>A LRG_292t1:c.1912G>A LRG_292p1:p.Glu638Lys U14680.1:n.2031G>A - Protein change
- E638K, E591K, E470K, E511K, E596K, E611K, E635K, E526K, E550K, E590K, E597K, E510K, E549K, E568K, E570K, E571K, E612K, E637K, E342K, E527K, E567K
- Other names
-
2031G>A
- Canonical SPDI
- NC_000017.11:43093618: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.
- -
- 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 |
13071 | 14880 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (4) |
no assertion criteria provided
|
Sep 1, 2023 | RCV000031014.8 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Nov 17, 2023 | RCV000776222.9 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 25, 2023 | RCV001307829.8 | |
| Benign (1) |
criteria provided, single submitter
|
May 4, 2022 | RCV002247401.2 |
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. |
|
|---|---|---|---|---|---|
|
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: SCV003849642.1
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).
|
|
|
Uncertain significance
(Apr 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001497255.4
First in ClinVar: Mar 07, 2021 Last updated: Feb 28, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 37433). This missense change has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 30254663). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 638 of the BRCA1 protein (p.Glu638Lys). (less)
|
|
|
Likely benign
(Apr 18, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000911411.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
|
Benign
(May 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV002516980.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
|
|
|
Uncertain significance
(Nov 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002720579.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.E638K variant (also known as c.1912G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.E638K variant (also known as c.1912G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1912. The glutamic acid at codon 638 is replaced by lysine, an amino acid with similar properties. In one study, this alteration was detected in one family from a cohort of 1045 Italian patients who met BRCA1/2 testing criteria (Zuntini R et al. Front Genet, 2018 Sep;9:378). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Jul 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000189890.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
|
|
Uncertain significance
(Dec 22, 2010)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053607.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
|
|
|
Benign
(Sep 01, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical and Surgical Sciences, University of Bologna
Accession: SCV004228337.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
PM2(Supporting)+BS3(Strong)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
|
|
|
Uncertain significance
(May 21, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144246.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian Non Hispanic
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
|
Comment:
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 37433). This missense change has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 30254663). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 638 of the BRCA1 protein (p.Glu638Lys).
Comment:
The p.E638K variant (also known as c.1912G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1912. The glutamic acid at codon 638 is replaced by lysine, an amino acid with similar properties. In one study, this alteration was detected in one family from a cohort of 1045 Italian patients who met BRCA1/2 testing criteria (Zuntini R et al. Front Genet, 2018 Sep;9:378). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
PM2(Supporting)+BS3(Strong)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
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:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 37433). This missense change has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 30254663). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 638 of the BRCA1 protein (p.Glu638Lys).
Comment:
The p.E638K variant (also known as c.1912G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1912. The glutamic acid at codon 638 is replaced by lysine, an amino acid with similar properties. In one study, this alteration was detected in one family from a cohort of 1045 Italian patients who met BRCA1/2 testing criteria (Zuntini R et al. Front Genet, 2018 Sep;9:378). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
PM2(Supporting)+BS3(Strong)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help? | Zuntini R | Frontiers in genetics | 2018 | PMID: 30254663 |
| Missense variants of uncertain significance (VUS) altering the phosphorylation patterns of BRCA1 and BRCA2. | Tram E | PloS one | 2013 | PMID: 23704879 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
Text-mined citations for rs80357005 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 08, 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.