ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5423T>C (p.Val1808Ala)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5423T>C (p.Val1808Ala)
Variation ID: 55572 Accession: VCV000055572.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43047687 (GRCh38) [ NCBI UCSC ] 17: 41199704 (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 Jun 30, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5423T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Val1808Ala missense NM_001407571.1:c.5210T>C NP_001394500.1:p.Val1737Ala missense NM_001407581.1:c.5489T>C NP_001394510.1:p.Val1830Ala missense NM_001407582.1:c.5489T>C NP_001394511.1:p.Val1830Ala missense NM_001407583.1:c.5486T>C NP_001394512.1:p.Val1829Ala missense NM_001407585.1:c.5486T>C NP_001394514.1:p.Val1829Ala missense NM_001407587.1:c.5486T>C NP_001394516.1:p.Val1829Ala missense NM_001407590.1:c.5483T>C NP_001394519.1:p.Val1828Ala missense NM_001407591.1:c.5483T>C NP_001394520.1:p.Val1828Ala missense NM_001407593.1:c.5423T>C NP_001394522.1:p.Val1808Ala missense NM_001407594.1:c.5423T>C NP_001394523.1:p.Val1808Ala missense NM_001407596.1:c.5423T>C NP_001394525.1:p.Val1808Ala missense NM_001407597.1:c.5423T>C NP_001394526.1:p.Val1808Ala missense NM_001407598.1:c.5423T>C NP_001394527.1:p.Val1808Ala missense NM_001407602.1:c.5423T>C NP_001394531.1:p.Val1808Ala missense NM_001407603.1:c.5423T>C NP_001394532.1:p.Val1808Ala missense NM_001407605.1:c.5423T>C NP_001394534.1:p.Val1808Ala missense NM_001407610.1:c.5420T>C NP_001394539.1:p.Val1807Ala missense NM_001407611.1:c.5420T>C NP_001394540.1:p.Val1807Ala missense NM_001407612.1:c.5420T>C NP_001394541.1:p.Val1807Ala missense NM_001407613.1:c.5420T>C NP_001394542.1:p.Val1807Ala missense NM_001407614.1:c.5420T>C NP_001394543.1:p.Val1807Ala missense NM_001407615.1:c.5420T>C NP_001394544.1:p.Val1807Ala missense NM_001407616.1:c.5420T>C NP_001394545.1:p.Val1807Ala missense NM_001407617.1:c.5420T>C NP_001394546.1:p.Val1807Ala missense NM_001407618.1:c.5420T>C NP_001394547.1:p.Val1807Ala missense NM_001407619.1:c.5420T>C NP_001394548.1:p.Val1807Ala missense NM_001407620.1:c.5420T>C NP_001394549.1:p.Val1807Ala missense NM_001407621.1:c.5420T>C NP_001394550.1:p.Val1807Ala missense NM_001407622.1:c.5420T>C NP_001394551.1:p.Val1807Ala missense NM_001407623.1:c.5420T>C NP_001394552.1:p.Val1807Ala missense NM_001407624.1:c.5420T>C NP_001394553.1:p.Val1807Ala missense NM_001407625.1:c.5420T>C NP_001394554.1:p.Val1807Ala missense NM_001407626.1:c.5420T>C NP_001394555.1:p.Val1807Ala missense NM_001407627.1:c.5417T>C NP_001394556.1:p.Val1806Ala missense NM_001407628.1:c.5417T>C NP_001394557.1:p.Val1806Ala missense NM_001407629.1:c.5417T>C NP_001394558.1:p.Val1806Ala missense NM_001407630.1:c.5417T>C NP_001394559.1:p.Val1806Ala missense NM_001407631.1:c.5417T>C NP_001394560.1:p.Val1806Ala missense NM_001407632.1:c.5417T>C NP_001394561.1:p.Val1806Ala missense NM_001407633.1:c.5417T>C NP_001394562.1:p.Val1806Ala missense NM_001407634.1:c.5417T>C NP_001394563.1:p.Val1806Ala missense NM_001407635.1:c.5417T>C NP_001394564.1:p.Val1806Ala missense NM_001407636.1:c.5417T>C NP_001394565.1:p.Val1806Ala missense NM_001407637.1:c.5417T>C NP_001394566.1:p.Val1806Ala missense NM_001407638.1:c.5417T>C NP_001394567.1:p.Val1806Ala missense NM_001407639.1:c.5417T>C NP_001394568.1:p.Val1806Ala missense NM_001407640.1:c.5417T>C NP_001394569.1:p.Val1806Ala missense NM_001407641.1:c.5417T>C NP_001394570.1:p.Val1806Ala missense NM_001407642.1:c.5417T>C NP_001394571.1:p.Val1806Ala missense NM_001407644.1:c.5414T>C NP_001394573.1:p.Val1805Ala missense NM_001407645.1:c.5414T>C NP_001394574.1:p.Val1805Ala missense NM_001407646.1:c.5411T>C NP_001394575.1:p.Val1804Ala missense NM_001407647.1:c.5408T>C NP_001394576.1:p.Val1803Ala missense NM_001407648.1:c.5366T>C NP_001394577.1:p.Val1789Ala missense NM_001407649.1:c.5363T>C NP_001394578.1:p.Val1788Ala missense NM_001407652.1:c.5345T>C NP_001394581.1:p.Val1782Ala missense NM_001407653.1:c.5345T>C NP_001394582.1:p.Val1782Ala missense NM_001407654.1:c.5345T>C NP_001394583.1:p.Val1782Ala missense NM_001407655.1:c.5345T>C NP_001394584.1:p.Val1782Ala missense NM_001407656.1:c.5342T>C NP_001394585.1:p.Val1781Ala missense NM_001407657.1:c.5342T>C NP_001394586.1:p.Val1781Ala missense NM_001407658.1:c.5342T>C NP_001394587.1:p.Val1781Ala missense NM_001407659.1:c.5339T>C NP_001394588.1:p.Val1780Ala missense NM_001407660.1:c.5339T>C NP_001394589.1:p.Val1780Ala missense NM_001407661.1:c.5339T>C NP_001394590.1:p.Val1780Ala missense NM_001407662.1:c.5339T>C NP_001394591.1:p.Val1780Ala missense NM_001407663.1:c.5339T>C NP_001394592.1:p.Val1780Ala missense NM_001407664.1:c.5300T>C NP_001394593.1:p.Val1767Ala missense NM_001407665.1:c.5300T>C NP_001394594.1:p.Val1767Ala missense NM_001407666.1:c.5300T>C NP_001394595.1:p.Val1767Ala missense NM_001407667.1:c.5300T>C NP_001394596.1:p.Val1767Ala missense NM_001407668.1:c.5300T>C NP_001394597.1:p.Val1767Ala missense NM_001407669.1:c.5300T>C NP_001394598.1:p.Val1767Ala missense NM_001407670.1:c.5297T>C NP_001394599.1:p.Val1766Ala missense NM_001407671.1:c.5297T>C NP_001394600.1:p.Val1766Ala missense NM_001407672.1:c.5297T>C NP_001394601.1:p.Val1766Ala missense NM_001407673.1:c.5297T>C NP_001394602.1:p.Val1766Ala missense NM_001407674.1:c.5297T>C NP_001394603.1:p.Val1766Ala missense NM_001407675.1:c.5297T>C NP_001394604.1:p.Val1766Ala missense NM_001407676.1:c.5297T>C NP_001394605.1:p.Val1766Ala missense NM_001407677.1:c.5297T>C NP_001394606.1:p.Val1766Ala missense NM_001407678.1:c.5297T>C NP_001394607.1:p.Val1766Ala missense NM_001407679.1:c.5297T>C NP_001394608.1:p.Val1766Ala missense NM_001407680.1:c.5297T>C NP_001394609.1:p.Val1766Ala missense NM_001407681.1:c.5294T>C NP_001394610.1:p.Val1765Ala missense NM_001407682.1:c.5294T>C NP_001394611.1:p.Val1765Ala missense NM_001407683.1:c.5294T>C NP_001394612.1:p.Val1765Ala missense NM_001407684.1:c.5294T>C NP_001394613.1:p.Val1765Ala missense NM_001407685.1:c.5294T>C NP_001394614.1:p.Val1765Ala missense NM_001407686.1:c.5294T>C NP_001394615.1:p.Val1765Ala missense NM_001407687.1:c.5294T>C NP_001394616.1:p.Val1765Ala missense NM_001407688.1:c.5294T>C NP_001394617.1:p.Val1765Ala missense NM_001407689.1:c.5294T>C NP_001394618.1:p.Val1765Ala missense NM_001407690.1:c.5291T>C NP_001394619.1:p.Val1764Ala missense NM_001407691.1:c.5291T>C NP_001394620.1:p.Val1764Ala missense NM_001407692.1:c.5282T>C NP_001394621.1:p.Val1761Ala missense NM_001407694.1:c.5282T>C NP_001394623.1:p.Val1761Ala missense NM_001407695.1:c.5282T>C NP_001394624.1:p.Val1761Ala missense NM_001407696.1:c.5282T>C NP_001394625.1:p.Val1761Ala missense NM_001407697.1:c.5282T>C NP_001394626.1:p.Val1761Ala missense NM_001407698.1:c.5282T>C NP_001394627.1:p.Val1761Ala missense NM_001407724.1:c.5282T>C NP_001394653.1:p.Val1761Ala missense NM_001407725.1:c.5282T>C NP_001394654.1:p.Val1761Ala missense NM_001407726.1:c.5282T>C NP_001394655.1:p.Val1761Ala missense NM_001407727.1:c.5282T>C NP_001394656.1:p.Val1761Ala missense NM_001407728.1:c.5282T>C NP_001394657.1:p.Val1761Ala missense NM_001407729.1:c.5282T>C NP_001394658.1:p.Val1761Ala missense NM_001407730.1:c.5282T>C NP_001394659.1:p.Val1761Ala missense NM_001407731.1:c.5282T>C NP_001394660.1:p.Val1761Ala missense NM_001407732.1:c.5279T>C NP_001394661.1:p.Val1760Ala missense NM_001407733.1:c.5279T>C NP_001394662.1:p.Val1760Ala missense NM_001407734.1:c.5279T>C NP_001394663.1:p.Val1760Ala missense NM_001407735.1:c.5279T>C NP_001394664.1:p.Val1760Ala missense NM_001407736.1:c.5279T>C NP_001394665.1:p.Val1760Ala missense NM_001407737.1:c.5279T>C NP_001394666.1:p.Val1760Ala missense NM_001407738.1:c.5279T>C NP_001394667.1:p.Val1760Ala missense NM_001407739.1:c.5279T>C NP_001394668.1:p.Val1760Ala missense NM_001407740.1:c.5279T>C NP_001394669.1:p.Val1760Ala missense NM_001407741.1:c.5279T>C NP_001394670.1:p.Val1760Ala missense NM_001407742.1:c.5279T>C NP_001394671.1:p.Val1760Ala missense NM_001407743.1:c.5279T>C NP_001394672.1:p.Val1760Ala missense NM_001407744.1:c.5279T>C NP_001394673.1:p.Val1760Ala missense NM_001407745.1:c.5279T>C NP_001394674.1:p.Val1760Ala missense NM_001407746.1:c.5279T>C NP_001394675.1:p.Val1760Ala missense NM_001407747.1:c.5279T>C NP_001394676.1:p.Val1760Ala missense NM_001407748.1:c.5279T>C NP_001394677.1:p.Val1760Ala missense NM_001407749.1:c.5279T>C NP_001394678.1:p.Val1760Ala missense NM_001407750.1:c.5279T>C NP_001394679.1:p.Val1760Ala missense NM_001407751.1:c.5279T>C NP_001394680.1:p.Val1760Ala missense NM_001407752.1:c.5279T>C NP_001394681.1:p.Val1760Ala missense NM_001407838.1:c.5276T>C NP_001394767.1:p.Val1759Ala missense NM_001407839.1:c.5276T>C NP_001394768.1:p.Val1759Ala missense NM_001407841.1:c.5276T>C NP_001394770.1:p.Val1759Ala missense NM_001407842.1:c.5276T>C NP_001394771.1:p.Val1759Ala missense NM_001407843.1:c.5276T>C NP_001394772.1:p.Val1759Ala missense NM_001407844.1:c.5276T>C NP_001394773.1:p.Val1759Ala missense NM_001407845.1:c.5276T>C NP_001394774.1:p.Val1759Ala missense NM_001407846.1:c.5276T>C NP_001394775.1:p.Val1759Ala missense NM_001407847.1:c.5276T>C NP_001394776.1:p.Val1759Ala missense NM_001407848.1:c.5276T>C NP_001394777.1:p.Val1759Ala missense NM_001407849.1:c.5276T>C NP_001394778.1:p.Val1759Ala missense NM_001407850.1:c.5276T>C NP_001394779.1:p.Val1759Ala missense NM_001407851.1:c.5276T>C NP_001394780.1:p.Val1759Ala missense NM_001407852.1:c.5276T>C NP_001394781.1:p.Val1759Ala missense NM_001407853.1:c.5276T>C NP_001394782.1:p.Val1759Ala missense NM_001407854.1:c.5349T>C NP_001394783.1:p.Cys1783= synonymous NM_001407858.1:c.5346T>C NP_001394787.1:p.Cys1782= synonymous NM_001407859.1:c.5346T>C NP_001394788.1:p.Cys1782= synonymous NM_001407860.1:c.5346T>C NP_001394789.1:p.Cys1782= synonymous NM_001407861.1:c.5343T>C NP_001394790.1:p.Cys1781= synonymous NM_001407862.1:c.5222T>C NP_001394791.1:p.Val1741Ala missense NM_001407863.1:c.5219T>C NP_001394792.1:p.Val1740Ala missense NM_001407874.1:c.5216T>C NP_001394803.1:p.Val1739Ala missense NM_001407875.1:c.5216T>C NP_001394804.1:p.Val1739Ala missense NM_001407879.1:c.5213T>C NP_001394808.1:p.Val1738Ala missense NM_001407881.1:c.5213T>C NP_001394810.1:p.Val1738Ala missense NM_001407882.1:c.5213T>C NP_001394811.1:p.Val1738Ala missense NM_001407884.1:c.5213T>C NP_001394813.1:p.Val1738Ala missense NM_001407885.1:c.5213T>C NP_001394814.1:p.Val1738Ala missense NM_001407886.1:c.5213T>C NP_001394815.1:p.Val1738Ala missense NM_001407887.1:c.5213T>C NP_001394816.1:p.Val1738Ala missense NM_001407889.1:c.5213T>C NP_001394818.1:p.Val1738Ala missense NM_001407894.1:c.5210T>C NP_001394823.1:p.Val1737Ala missense NM_001407895.1:c.5210T>C NP_001394824.1:p.Val1737Ala missense NM_001407896.1:c.5210T>C NP_001394825.1:p.Val1737Ala missense NM_001407897.1:c.5210T>C NP_001394826.1:p.Val1737Ala missense NM_001407898.1:c.5210T>C NP_001394827.1:p.Val1737Ala missense NM_001407899.1:c.5210T>C NP_001394828.1:p.Val1737Ala missense NM_001407900.1:c.5210T>C NP_001394829.1:p.Val1737Ala missense NM_001407902.1:c.5210T>C NP_001394831.1:p.Val1737Ala missense NM_001407904.1:c.5210T>C NP_001394833.1:p.Val1737Ala missense NM_001407906.1:c.5210T>C NP_001394835.1:p.Val1737Ala missense NM_001407907.1:c.5210T>C NP_001394836.1:p.Val1737Ala missense NM_001407908.1:c.5210T>C NP_001394837.1:p.Val1737Ala missense NM_001407909.1:c.5210T>C NP_001394838.1:p.Val1737Ala missense NM_001407910.1:c.5210T>C NP_001394839.1:p.Val1737Ala missense NM_001407915.1:c.5207T>C NP_001394844.1:p.Val1736Ala missense NM_001407916.1:c.5207T>C NP_001394845.1:p.Val1736Ala missense NM_001407917.1:c.5207T>C NP_001394846.1:p.Val1736Ala missense NM_001407918.1:c.5207T>C NP_001394847.1:p.Val1736Ala missense NM_001407919.1:c.5171T>C NP_001394848.1:p.Val1724Ala missense NM_001407920.1:c.5159T>C NP_001394849.1:p.Val1720Ala missense NM_001407921.1:c.5159T>C NP_001394850.1:p.Val1720Ala missense NM_001407922.1:c.5159T>C NP_001394851.1:p.Val1720Ala missense NM_001407923.1:c.5159T>C NP_001394852.1:p.Val1720Ala missense NM_001407924.1:c.5159T>C NP_001394853.1:p.Val1720Ala missense NM_001407925.1:c.5159T>C NP_001394854.1:p.Val1720Ala missense NM_001407926.1:c.5159T>C NP_001394855.1:p.Val1720Ala missense NM_001407927.1:c.5156T>C NP_001394856.1:p.Val1719Ala missense NM_001407928.1:c.5156T>C NP_001394857.1:p.Val1719Ala missense NM_001407929.1:c.5156T>C NP_001394858.1:p.Val1719Ala missense NM_001407930.1:c.5156T>C NP_001394859.1:p.Val1719Ala missense NM_001407931.1:c.5156T>C NP_001394860.1:p.Val1719Ala missense NM_001407932.1:c.5156T>C NP_001394861.1:p.Val1719Ala missense NM_001407933.1:c.5156T>C NP_001394862.1:p.Val1719Ala missense NM_001407934.1:c.5153T>C NP_001394863.1:p.Val1718Ala missense NM_001407935.1:c.5153T>C NP_001394864.1:p.Val1718Ala missense NM_001407936.1:c.5153T>C NP_001394865.1:p.Val1718Ala missense NM_001407937.1:c.5226T>C NP_001394866.1:p.Cys1742= synonymous NM_001407938.1:c.5226T>C NP_001394867.1:p.Cys1742= synonymous NM_001407939.1:c.5223T>C NP_001394868.1:p.Cys1741= synonymous NM_001407940.1:c.5223T>C NP_001394869.1:p.Cys1741= synonymous NM_001407941.1:c.5220T>C NP_001394870.1:p.Cys1740= synonymous NM_001407942.1:c.5208T>C NP_001394871.1:p.Cys1736= synonymous NM_001407943.1:c.5205T>C NP_001394872.1:p.Cys1735= synonymous NM_001407944.1:c.5205T>C NP_001394873.1:p.Cys1735= synonymous NM_001407945.1:c.5205T>C NP_001394874.1:p.Cys1735= synonymous NM_001407946.1:c.5090T>C NP_001394875.1:p.Val1697Ala missense NM_001407947.1:c.5090T>C NP_001394876.1:p.Val1697Ala missense NM_001407948.1:c.5090T>C NP_001394877.1:p.Val1697Ala missense NM_001407949.1:c.5090T>C NP_001394878.1:p.Val1697Ala missense NM_001407950.1:c.5087T>C NP_001394879.1:p.Val1696Ala missense NM_001407951.1:c.5087T>C NP_001394880.1:p.Val1696Ala missense NM_001407952.1:c.5087T>C NP_001394881.1:p.Val1696Ala missense NM_001407953.1:c.5087T>C NP_001394882.1:p.Val1696Ala missense NM_001407954.1:c.5087T>C NP_001394883.1:p.Val1696Ala missense NM_001407955.1:c.5087T>C NP_001394884.1:p.Val1696Ala missense NM_001407956.1:c.5084T>C NP_001394885.1:p.Val1695Ala missense NM_001407957.1:c.5084T>C NP_001394886.1:p.Val1695Ala missense NM_001407958.1:c.5084T>C NP_001394887.1:p.Val1695Ala missense NM_001407959.1:c.5042T>C NP_001394888.1:p.Val1681Ala missense NM_001407960.1:c.5039T>C NP_001394889.1:p.Val1680Ala missense NM_001407962.1:c.5039T>C NP_001394891.1:p.Val1680Ala missense NM_001407963.1:c.5036T>C NP_001394892.1:p.Val1679Ala missense NM_001407964.1:c.4961T>C NP_001394893.1:p.Val1654Ala missense NM_001407965.1:c.4916T>C NP_001394894.1:p.Val1639Ala missense NM_001407966.1:c.4535T>C NP_001394895.1:p.Val1512Ala missense NM_001407967.1:c.4532T>C NP_001394896.1:p.Val1511Ala missense NM_001407968.1:c.2819T>C NP_001394897.1:p.Val940Ala missense NM_001407969.1:c.2816T>C NP_001394898.1:p.Val939Ala missense NM_001407970.1:c.2180T>C NP_001394899.1:p.Val727Ala missense NM_001407971.1:c.2180T>C NP_001394900.1:p.Val727Ala missense NM_001407972.1:c.2177T>C NP_001394901.1:p.Val726Ala missense NM_001407973.1:c.2114T>C NP_001394902.1:p.Val705Ala missense NM_001407974.1:c.2114T>C NP_001394903.1:p.Val705Ala missense NM_001407975.1:c.2114T>C NP_001394904.1:p.Val705Ala missense NM_001407976.1:c.2114T>C NP_001394905.1:p.Val705Ala missense NM_001407977.1:c.2114T>C NP_001394906.1:p.Val705Ala missense NM_001407978.1:c.2114T>C NP_001394907.1:p.Val705Ala missense NM_001407979.1:c.2111T>C NP_001394908.1:p.Val704Ala missense NM_001407980.1:c.2111T>C NP_001394909.1:p.Val704Ala missense NM_001407981.1:c.2111T>C NP_001394910.1:p.Val704Ala missense NM_001407982.1:c.2111T>C NP_001394911.1:p.Val704Ala missense NM_001407983.1:c.2111T>C NP_001394912.1:p.Val704Ala missense NM_001407984.1:c.2111T>C NP_001394913.1:p.Val704Ala missense NM_001407985.1:c.2111T>C NP_001394914.1:p.Val704Ala missense NM_001407986.1:c.2111T>C NP_001394915.1:p.Val704Ala missense NM_001407990.1:c.2111T>C NP_001394919.1:p.Val704Ala missense NM_001407991.1:c.2111T>C NP_001394920.1:p.Val704Ala missense NM_001407992.1:c.2111T>C NP_001394921.1:p.Val704Ala missense NM_001407993.1:c.2111T>C NP_001394922.1:p.Val704Ala missense NM_001408392.1:c.2108T>C NP_001395321.1:p.Val703Ala missense NM_001408396.1:c.2108T>C NP_001395325.1:p.Val703Ala missense NM_001408397.1:c.2108T>C NP_001395326.1:p.Val703Ala missense NM_001408398.1:c.2108T>C NP_001395327.1:p.Val703Ala missense NM_001408399.1:c.2108T>C NP_001395328.1:p.Val703Ala missense NM_001408400.1:c.2108T>C NP_001395329.1:p.Val703Ala missense NM_001408401.1:c.2108T>C NP_001395330.1:p.Val703Ala missense NM_001408402.1:c.2108T>C NP_001395331.1:p.Val703Ala missense NM_001408403.1:c.2108T>C NP_001395332.1:p.Val703Ala missense NM_001408404.1:c.2108T>C NP_001395333.1:p.Val703Ala missense NM_001408406.1:c.2105T>C NP_001395335.1:p.Val702Ala missense NM_001408407.1:c.2105T>C NP_001395336.1:p.Val702Ala missense NM_001408408.1:c.2105T>C NP_001395337.1:p.Val702Ala missense NM_001408409.1:c.2102T>C NP_001395338.1:p.Val701Ala missense NM_001408410.1:c.2039T>C NP_001395339.1:p.Val680Ala missense NM_001408411.1:c.2036T>C NP_001395340.1:p.Val679Ala missense NM_001408412.1:c.2033T>C NP_001395341.1:p.Val678Ala missense NM_001408413.1:c.2033T>C NP_001395342.1:p.Val678Ala missense NM_001408414.1:c.2033T>C NP_001395343.1:p.Val678Ala missense NM_001408415.1:c.2033T>C NP_001395344.1:p.Val678Ala missense NM_001408416.1:c.2033T>C NP_001395345.1:p.Val678Ala missense NM_001408418.1:c.1997T>C NP_001395347.1:p.Val666Ala missense NM_001408419.1:c.1997T>C NP_001395348.1:p.Val666Ala missense NM_001408420.1:c.1997T>C NP_001395349.1:p.Val666Ala missense NM_001408421.1:c.1994T>C NP_001395350.1:p.Val665Ala missense NM_001408422.1:c.1994T>C NP_001395351.1:p.Val665Ala missense NM_001408423.1:c.1994T>C NP_001395352.1:p.Val665Ala missense NM_001408424.1:c.1994T>C NP_001395353.1:p.Val665Ala missense NM_001408425.1:c.1991T>C NP_001395354.1:p.Val664Ala missense NM_001408426.1:c.1991T>C NP_001395355.1:p.Val664Ala missense NM_001408427.1:c.1991T>C NP_001395356.1:p.Val664Ala missense NM_001408428.1:c.1991T>C NP_001395357.1:p.Val664Ala missense NM_001408429.1:c.1991T>C NP_001395358.1:p.Val664Ala missense NM_001408430.1:c.1991T>C NP_001395359.1:p.Val664Ala missense NM_001408431.1:c.1991T>C NP_001395360.1:p.Val664Ala missense NM_001408432.1:c.1988T>C NP_001395361.1:p.Val663Ala missense NM_001408433.1:c.1988T>C NP_001395362.1:p.Val663Ala missense NM_001408434.1:c.1988T>C NP_001395363.1:p.Val663Ala missense NM_001408435.1:c.1988T>C NP_001395364.1:p.Val663Ala missense NM_001408436.1:c.1988T>C NP_001395365.1:p.Val663Ala missense NM_001408437.1:c.1988T>C NP_001395366.1:p.Val663Ala missense NM_001408438.1:c.1988T>C NP_001395367.1:p.Val663Ala missense NM_001408439.1:c.1988T>C NP_001395368.1:p.Val663Ala missense NM_001408440.1:c.1988T>C NP_001395369.1:p.Val663Ala missense NM_001408441.1:c.1988T>C NP_001395370.1:p.Val663Ala missense NM_001408442.1:c.1988T>C NP_001395371.1:p.Val663Ala missense NM_001408443.1:c.1988T>C NP_001395372.1:p.Val663Ala missense NM_001408444.1:c.1988T>C NP_001395373.1:p.Val663Ala missense NM_001408445.1:c.1985T>C NP_001395374.1:p.Val662Ala missense NM_001408446.1:c.1985T>C NP_001395375.1:p.Val662Ala missense NM_001408447.1:c.1985T>C NP_001395376.1:p.Val662Ala missense NM_001408448.1:c.1985T>C NP_001395377.1:p.Val662Ala missense NM_001408450.1:c.1985T>C NP_001395379.1:p.Val662Ala missense NM_001408451.1:c.1979T>C NP_001395380.1:p.Val660Ala missense NM_001408452.1:c.1973T>C NP_001395381.1:p.Val658Ala missense NM_001408453.1:c.1973T>C NP_001395382.1:p.Val658Ala missense NM_001408454.1:c.1973T>C NP_001395383.1:p.Val658Ala missense NM_001408455.1:c.1973T>C NP_001395384.1:p.Val658Ala missense NM_001408456.1:c.1973T>C NP_001395385.1:p.Val658Ala missense NM_001408457.1:c.1973T>C NP_001395386.1:p.Val658Ala missense NM_001408458.1:c.1970T>C NP_001395387.1:p.Val657Ala missense NM_001408459.1:c.1970T>C NP_001395388.1:p.Val657Ala missense NM_001408460.1:c.1970T>C NP_001395389.1:p.Val657Ala missense NM_001408461.1:c.1970T>C NP_001395390.1:p.Val657Ala missense NM_001408462.1:c.1970T>C NP_001395391.1:p.Val657Ala missense NM_001408463.1:c.1970T>C NP_001395392.1:p.Val657Ala missense NM_001408464.1:c.1970T>C NP_001395393.1:p.Val657Ala missense NM_001408465.1:c.1970T>C NP_001395394.1:p.Val657Ala missense NM_001408466.1:c.1970T>C NP_001395395.1:p.Val657Ala missense NM_001408467.1:c.1970T>C NP_001395396.1:p.Val657Ala missense NM_001408468.1:c.1967T>C NP_001395397.1:p.Val656Ala missense NM_001408469.1:c.1967T>C NP_001395398.1:p.Val656Ala missense NM_001408470.1:c.1967T>C NP_001395399.1:p.Val656Ala missense NM_001408472.1:c.2037T>C NP_001395401.1:p.Cys679= synonymous NM_001408473.1:c.2034T>C NP_001395402.1:p.Cys678= synonymous NM_001408474.1:c.1913T>C NP_001395403.1:p.Val638Ala missense NM_001408475.1:c.1910T>C NP_001395404.1:p.Val637Ala missense NM_001408476.1:c.1910T>C NP_001395405.1:p.Val637Ala missense NM_001408478.1:c.1904T>C NP_001395407.1:p.Val635Ala missense NM_001408479.1:c.1904T>C NP_001395408.1:p.Val635Ala missense NM_001408480.1:c.1904T>C NP_001395409.1:p.Val635Ala missense NM_001408481.1:c.1901T>C NP_001395410.1:p.Val634Ala missense NM_001408482.1:c.1901T>C NP_001395411.1:p.Val634Ala missense NM_001408483.1:c.1901T>C NP_001395412.1:p.Val634Ala missense NM_001408484.1:c.1901T>C NP_001395413.1:p.Val634Ala missense NM_001408485.1:c.1901T>C NP_001395414.1:p.Val634Ala missense NM_001408489.1:c.1901T>C NP_001395418.1:p.Val634Ala missense NM_001408490.1:c.1901T>C NP_001395419.1:p.Val634Ala missense NM_001408491.1:c.1901T>C NP_001395420.1:p.Val634Ala missense NM_001408492.1:c.1898T>C NP_001395421.1:p.Val633Ala missense NM_001408493.1:c.1898T>C NP_001395422.1:p.Val633Ala missense NM_001408494.1:c.1874T>C NP_001395423.1:p.Val625Ala missense NM_001408495.1:c.1868T>C NP_001395424.1:p.Val623Ala missense NM_001408496.1:c.1850T>C NP_001395425.1:p.Val617Ala missense NM_001408497.1:c.1850T>C NP_001395426.1:p.Val617Ala missense NM_001408498.1:c.1850T>C NP_001395427.1:p.Val617Ala missense NM_001408499.1:c.1850T>C NP_001395428.1:p.Val617Ala missense NM_001408500.1:c.1850T>C NP_001395429.1:p.Val617Ala missense NM_001408501.1:c.1850T>C NP_001395430.1:p.Val617Ala missense NM_001408502.1:c.1847T>C NP_001395431.1:p.Val616Ala missense NM_001408503.1:c.1847T>C NP_001395432.1:p.Val616Ala missense NM_001408504.1:c.1847T>C NP_001395433.1:p.Val616Ala missense NM_001408505.1:c.1844T>C NP_001395434.1:p.Val615Ala missense NM_001408506.1:c.1787T>C NP_001395435.1:p.Val596Ala missense NM_001408507.1:c.1784T>C NP_001395436.1:p.Val595Ala missense NM_001408508.1:c.1775T>C NP_001395437.1:p.Val592Ala missense NM_001408509.1:c.1772T>C NP_001395438.1:p.Val591Ala missense NM_001408510.1:c.1733T>C NP_001395439.1:p.Val578Ala missense NM_001408511.1:c.1730T>C NP_001395440.1:p.Val577Ala missense NM_001408512.1:c.1610T>C NP_001395441.1:p.Val537Ala missense NM_001408513.1:c.1583T>C NP_001395442.1:p.Val528Ala missense NM_001408514.1:c.1187T>C NP_001395443.1:p.Val396Ala missense NM_007297.4:c.5282T>C NP_009228.2:p.Val1761Ala missense NM_007298.4:c.2111T>C NP_009229.2:p.Val704Ala missense NM_007299.4:c.2037T>C NP_009230.2:p.Cys679= synonymous NM_007300.3:c.5486T>C NM_007300.4:c.5486T>C NP_009231.2:p.Val1829Ala missense NM_007304.2:c.2111T>C NP_009235.2:p.Val704Ala missense NR_027676.2:n.5600T>C NC_000017.11:g.43047687A>G NC_000017.10:g.41199704A>G NG_005905.2:g.170297T>C LRG_292:g.170297T>C LRG_292t1:c.5423T>C LRG_292p1:p.Val1808Ala U14680.1:n.5542T>C - Protein change
- V1808A, V1761A, V1829A, V704A, V1512A, V1695A, V1719A, V1720A, V1724A, V1738A, V1780A, V1828A, V591A, V617A, V633A, V638A, V663A, V701A, V939A, V1696A, V1697A, V1718A, V1737A, V1740A, V1764A, V1766A, V1767A, V1804A, V1805A, V1807A, V396A, V577A, V592A, V596A, V616A, V634A, V657A, V665A, V666A, V680A, V702A, V1639A, V1654A, V1679A, V1736A, V1739A, V1759A, V1782A, V1788A, V1789A, V1803A, V1806A, V1830A, V528A, V595A, V623A, V637A, V656A, V662A, V664A, V678A, V703A, V940A, V1511A, V1680A, V1681A, V1741A, V1760A, V1765A, V1781A, V537A, V578A, V615A, V625A, V635A, V658A, V660A, V679A, V705A, V726A, V727A
- Other names
- -
- Canonical SPDI
- NC_000017.11:43047686:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- function_uncertain_variant Sequence Ontology [SO:0002220]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5423T>C, a MISSENSE variant, produced a function score of -0.8, corresponding to a functional classification of INTERMEDIATE. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
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.
-
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 |
12887 | 14672 |
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. |
---|---|---|---|---|
Uncertain significance (4) |
criteria provided, single submitter
|
Jun 30, 2023 | RCV000112650.6 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 26, 2023 | RCV001024082.9 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Aug 13, 2021 | RCV001338089.6 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Aug 13, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001531729.3
First in ClinVar: Mar 22, 2021 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces valine with alanine at codon 1808 of the BRCA1 protein (p.Val1808Ala). The valine residue is highly conserved and there is a … (more)
This sequence change replaces valine with alanine at codon 1808 of the BRCA1 protein (p.Val1808Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with BRCA1-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55572). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 14534301, 15004537, 20378548, 20516115). 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. (less)
|
|
Uncertain significance
(Jun 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004215076.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Uncertain significance
(Jan 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001352266.2
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces valine with alanine at codon 1808 in the BRCT domain of the BRCA1 protein. Computational prediction suggests that this variant may … (more)
This missense variant replaces valine with alanine at codon 1808 in the BRCT domain of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant results in a moderately destabilized BRCA1 protein with a larger proportion of unfolded protein at physiological conditions in comparison to the wild type protein (PMID 20378548), and an intermediate function score (PMID 30209399). However, functional studies have also shown that the BRCA1 V1808A protein has proteolytic stability indistinguishable from the WT protein (PMID20516115). Functional studies in yeast have shown this variant causes a small colony phenotype, predictive of a negative impact on BRCA1 structure or function (PMID 15004537). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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)
|
|
Uncertain significance
(Mar 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001186040.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.V1808A variant (also known as c.5423T>C), located in coding exon 21 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.V1808A variant (also known as c.5423T>C), located in coding exon 21 of the BRCA1 gene, results from a T to C substitution at nucleotide position 5423. The valine at codon 1808 is replaced by alanine, an amino acid with similar properties. This alteration shows intermediate function in a haploid cell survival assay as well as a yeast small colony phenotype assay (Findlay GM et al. Nature, 2018 10;562:217-222; Coyne RS et al. Cancer Biol. Ther., 2004 May;3:453-7). Additional analysis shows no defect in protein folding, and uncertain functionality in terms of transcriptional activation, and protein binding (Lee MS et al. Cancer Res. 2010 Jun;70:4880-90). Several computational methods predict this alteration has at lease a moderate destabilizing effect on the protein (Rowling PJ et al. J. Biol. Chem., 2010 Jun;285:20080-7; Mirkovic N et al. Cancer Res., 2004 Jun;64:3790-7; Williams RS et al. J. Biol. Chem., 2003 Dec;278:53007-16). This amino acid position is highly 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
(Feb 15, 1997)
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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: SCV000145508.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
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Uncertain significance
(May 05, 2023)
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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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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV003927203.1
First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023 |
Comment:
A variant of uncertain significance was detected in this sample . This sequence change replaces valine with alanine at codon 1829 of the BRCA1 protein … (more)
A variant of uncertain significance was detected in this sample . This sequence change replaces valine with alanine at codon 1829 of the BRCA1 protein (p.Val1829Ala ) also known as c.5486T>C, which located in coding exon 23 of the BRCA1 gene(NM_007300.3), results from a T to C substitution at nucleotide position 5486. This amino acid position is highly conserved. This variant is not present in population databases (gnomAD ). This variant reported in ClinVar database (ID: 55572) . This alteration is predicted to be possibly damaging and deleterious by ( BayesDel_addAF, DANN, EIGEN, FATHMM-MKL, LIST-S2, M-CAP, MVP, MutationTaster and SIFT). The inviro function test shows intermediate function in a haploid cell survival assay (PMID: 30209399). Additional analysis shows uncertain functionality in terms of transcriptional activation and protein binding (PMID: 20516115). 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. (less)
Sex: female
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001238371.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
INTERMEDIATE:-0.798819225404382
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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function_uncertain_variant
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001238371.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5423T>C, a MISSENSE variant, produced a function score of -0.8, corresponding to a functional classification of INTERMEDIATE. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5423T>C, a MISSENSE variant, produced a function score of -0.8, corresponding to a functional classification of INTERMEDIATE. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Toward classification of BRCA1 missense variants using a biophysical approach. | Rowling PJ | The Journal of biological chemistry | 2010 | PMID: 20378548 |
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 |
Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition. | Mirkovic N | Cancer research | 2004 | PMID: 15172985 |
Functional characterization of BRCA1 sequence variants using a yeast small colony phenotype assay. | Coyne RS | Cancer biology & therapy | 2004 | PMID: 15004537 |
Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. | Williams RS | The Journal of biological chemistry | 2003 | PMID: 14534301 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs80357358 ...
HelpRecord last updated Jun 02, 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.