ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1786C>G (p.Leu596Val)
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(5); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.1786C>G (p.Leu596Val)
Variation ID: 54347 Accession: VCV000054347.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093745 (GRCh38) [ NCBI UCSC ] 17: 41245762 (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 Jan 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.1786C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu596Val missense NM_001407571.1:c.1573C>G NP_001394500.1:p.Leu525Val missense NM_001407581.1:c.1786C>G NP_001394510.1:p.Leu596Val missense NM_001407582.1:c.1786C>G NP_001394511.1:p.Leu596Val missense NM_001407583.1:c.1786C>G NP_001394512.1:p.Leu596Val missense NM_001407585.1:c.1786C>G NP_001394514.1:p.Leu596Val missense NM_001407587.1:c.1783C>G NP_001394516.1:p.Leu595Val missense NM_001407590.1:c.1783C>G NP_001394519.1:p.Leu595Val missense NM_001407591.1:c.1783C>G NP_001394520.1:p.Leu595Val missense NM_001407593.1:c.1786C>G NP_001394522.1:p.Leu596Val missense NM_001407594.1:c.1786C>G NP_001394523.1:p.Leu596Val missense NM_001407596.1:c.1786C>G NP_001394525.1:p.Leu596Val missense NM_001407597.1:c.1786C>G NP_001394526.1:p.Leu596Val missense NM_001407598.1:c.1786C>G NP_001394527.1:p.Leu596Val missense NM_001407602.1:c.1786C>G NP_001394531.1:p.Leu596Val missense NM_001407603.1:c.1786C>G NP_001394532.1:p.Leu596Val missense NM_001407605.1:c.1786C>G NP_001394534.1:p.Leu596Val missense NM_001407610.1:c.1783C>G NP_001394539.1:p.Leu595Val missense NM_001407611.1:c.1783C>G NP_001394540.1:p.Leu595Val missense NM_001407612.1:c.1783C>G NP_001394541.1:p.Leu595Val missense NM_001407613.1:c.1783C>G NP_001394542.1:p.Leu595Val missense NM_001407614.1:c.1783C>G NP_001394543.1:p.Leu595Val missense NM_001407615.1:c.1783C>G NP_001394544.1:p.Leu595Val missense NM_001407616.1:c.1786C>G NP_001394545.1:p.Leu596Val missense NM_001407617.1:c.1786C>G NP_001394546.1:p.Leu596Val missense NM_001407618.1:c.1786C>G NP_001394547.1:p.Leu596Val missense NM_001407619.1:c.1786C>G NP_001394548.1:p.Leu596Val missense NM_001407620.1:c.1786C>G NP_001394549.1:p.Leu596Val missense NM_001407621.1:c.1786C>G NP_001394550.1:p.Leu596Val missense NM_001407622.1:c.1786C>G NP_001394551.1:p.Leu596Val missense NM_001407623.1:c.1786C>G NP_001394552.1:p.Leu596Val missense NM_001407624.1:c.1786C>G NP_001394553.1:p.Leu596Val missense NM_001407625.1:c.1786C>G NP_001394554.1:p.Leu596Val missense NM_001407626.1:c.1786C>G NP_001394555.1:p.Leu596Val missense NM_001407627.1:c.1783C>G NP_001394556.1:p.Leu595Val missense NM_001407628.1:c.1783C>G NP_001394557.1:p.Leu595Val missense NM_001407629.1:c.1783C>G NP_001394558.1:p.Leu595Val missense NM_001407630.1:c.1783C>G NP_001394559.1:p.Leu595Val missense NM_001407631.1:c.1783C>G NP_001394560.1:p.Leu595Val missense NM_001407632.1:c.1783C>G NP_001394561.1:p.Leu595Val missense NM_001407633.1:c.1783C>G NP_001394562.1:p.Leu595Val missense NM_001407634.1:c.1783C>G NP_001394563.1:p.Leu595Val missense NM_001407635.1:c.1783C>G NP_001394564.1:p.Leu595Val missense NM_001407636.1:c.1783C>G NP_001394565.1:p.Leu595Val missense NM_001407637.1:c.1783C>G NP_001394566.1:p.Leu595Val missense NM_001407638.1:c.1783C>G NP_001394567.1:p.Leu595Val missense NM_001407639.1:c.1786C>G NP_001394568.1:p.Leu596Val missense NM_001407640.1:c.1786C>G NP_001394569.1:p.Leu596Val missense NM_001407641.1:c.1786C>G NP_001394570.1:p.Leu596Val missense NM_001407642.1:c.1786C>G NP_001394571.1:p.Leu596Val missense NM_001407644.1:c.1783C>G NP_001394573.1:p.Leu595Val missense NM_001407645.1:c.1783C>G NP_001394574.1:p.Leu595Val missense NM_001407646.1:c.1777C>G NP_001394575.1:p.Leu593Val missense NM_001407647.1:c.1777C>G NP_001394576.1:p.Leu593Val missense NM_001407648.1:c.1663C>G NP_001394577.1:p.Leu555Val missense NM_001407649.1:c.1660C>G NP_001394578.1:p.Leu554Val missense NM_001407652.1:c.1786C>G NP_001394581.1:p.Leu596Val missense NM_001407653.1:c.1708C>G NP_001394582.1:p.Leu570Val missense NM_001407654.1:c.1708C>G NP_001394583.1:p.Leu570Val missense NM_001407655.1:c.1708C>G NP_001394584.1:p.Leu570Val missense NM_001407656.1:c.1708C>G NP_001394585.1:p.Leu570Val missense NM_001407657.1:c.1708C>G NP_001394586.1:p.Leu570Val missense NM_001407658.1:c.1708C>G NP_001394587.1:p.Leu570Val missense NM_001407659.1:c.1705C>G NP_001394588.1:p.Leu569Val missense NM_001407660.1:c.1705C>G NP_001394589.1:p.Leu569Val missense NM_001407661.1:c.1705C>G NP_001394590.1:p.Leu569Val missense NM_001407662.1:c.1705C>G NP_001394591.1:p.Leu569Val missense NM_001407663.1:c.1708C>G NP_001394592.1:p.Leu570Val missense NM_001407664.1:c.1663C>G NP_001394593.1:p.Leu555Val missense NM_001407665.1:c.1663C>G NP_001394594.1:p.Leu555Val missense NM_001407666.1:c.1663C>G NP_001394595.1:p.Leu555Val missense NM_001407667.1:c.1663C>G NP_001394596.1:p.Leu555Val missense NM_001407668.1:c.1663C>G NP_001394597.1:p.Leu555Val missense NM_001407669.1:c.1663C>G NP_001394598.1:p.Leu555Val missense NM_001407670.1:c.1660C>G NP_001394599.1:p.Leu554Val missense NM_001407671.1:c.1660C>G NP_001394600.1:p.Leu554Val missense NM_001407672.1:c.1660C>G NP_001394601.1:p.Leu554Val missense NM_001407673.1:c.1660C>G NP_001394602.1:p.Leu554Val missense NM_001407674.1:c.1663C>G NP_001394603.1:p.Leu555Val missense NM_001407675.1:c.1663C>G NP_001394604.1:p.Leu555Val missense NM_001407676.1:c.1663C>G NP_001394605.1:p.Leu555Val missense NM_001407677.1:c.1663C>G NP_001394606.1:p.Leu555Val missense NM_001407678.1:c.1663C>G NP_001394607.1:p.Leu555Val missense NM_001407679.1:c.1663C>G NP_001394608.1:p.Leu555Val missense NM_001407680.1:c.1663C>G NP_001394609.1:p.Leu555Val missense NM_001407681.1:c.1663C>G NP_001394610.1:p.Leu555Val missense NM_001407682.1:c.1663C>G NP_001394611.1:p.Leu555Val missense NM_001407683.1:c.1663C>G NP_001394612.1:p.Leu555Val missense NM_001407684.1:c.1786C>G NP_001394613.1:p.Leu596Val missense NM_001407685.1:c.1660C>G NP_001394614.1:p.Leu554Val missense NM_001407686.1:c.1660C>G NP_001394615.1:p.Leu554Val missense NM_001407687.1:c.1660C>G NP_001394616.1:p.Leu554Val missense NM_001407688.1:c.1660C>G NP_001394617.1:p.Leu554Val missense NM_001407689.1:c.1660C>G NP_001394618.1:p.Leu554Val missense NM_001407690.1:c.1660C>G NP_001394619.1:p.Leu554Val missense NM_001407691.1:c.1660C>G NP_001394620.1:p.Leu554Val missense NM_001407692.1:c.1645C>G NP_001394621.1:p.Leu549Val missense NM_001407694.1:c.1645C>G NP_001394623.1:p.Leu549Val missense NM_001407695.1:c.1645C>G NP_001394624.1:p.Leu549Val missense NM_001407696.1:c.1645C>G NP_001394625.1:p.Leu549Val missense NM_001407697.1:c.1645C>G NP_001394626.1:p.Leu549Val missense NM_001407698.1:c.1645C>G NP_001394627.1:p.Leu549Val missense NM_001407724.1:c.1645C>G NP_001394653.1:p.Leu549Val missense NM_001407725.1:c.1645C>G NP_001394654.1:p.Leu549Val missense NM_001407726.1:c.1645C>G NP_001394655.1:p.Leu549Val missense NM_001407727.1:c.1645C>G NP_001394656.1:p.Leu549Val missense NM_001407728.1:c.1645C>G NP_001394657.1:p.Leu549Val missense NM_001407729.1:c.1645C>G NP_001394658.1:p.Leu549Val missense NM_001407730.1:c.1645C>G NP_001394659.1:p.Leu549Val missense NM_001407731.1:c.1645C>G NP_001394660.1:p.Leu549Val missense NM_001407732.1:c.1645C>G NP_001394661.1:p.Leu549Val missense NM_001407733.1:c.1645C>G NP_001394662.1:p.Leu549Val missense NM_001407734.1:c.1645C>G NP_001394663.1:p.Leu549Val missense NM_001407735.1:c.1645C>G NP_001394664.1:p.Leu549Val missense NM_001407736.1:c.1645C>G NP_001394665.1:p.Leu549Val missense NM_001407737.1:c.1645C>G NP_001394666.1:p.Leu549Val missense NM_001407738.1:c.1645C>G NP_001394667.1:p.Leu549Val missense NM_001407739.1:c.1645C>G NP_001394668.1:p.Leu549Val missense NM_001407740.1:c.1642C>G NP_001394669.1:p.Leu548Val missense NM_001407741.1:c.1642C>G NP_001394670.1:p.Leu548Val missense NM_001407742.1:c.1642C>G NP_001394671.1:p.Leu548Val missense NM_001407743.1:c.1642C>G NP_001394672.1:p.Leu548Val missense NM_001407744.1:c.1642C>G NP_001394673.1:p.Leu548Val missense NM_001407745.1:c.1642C>G NP_001394674.1:p.Leu548Val missense NM_001407746.1:c.1642C>G NP_001394675.1:p.Leu548Val missense NM_001407747.1:c.1642C>G NP_001394676.1:p.Leu548Val missense NM_001407748.1:c.1642C>G NP_001394677.1:p.Leu548Val missense NM_001407749.1:c.1642C>G NP_001394678.1:p.Leu548Val missense NM_001407750.1:c.1645C>G NP_001394679.1:p.Leu549Val missense NM_001407751.1:c.1645C>G NP_001394680.1:p.Leu549Val missense NM_001407752.1:c.1645C>G NP_001394681.1:p.Leu549Val missense NM_001407838.1:c.1642C>G NP_001394767.1:p.Leu548Val missense NM_001407839.1:c.1642C>G NP_001394768.1:p.Leu548Val missense NM_001407841.1:c.1642C>G NP_001394770.1:p.Leu548Val missense NM_001407842.1:c.1642C>G NP_001394771.1:p.Leu548Val missense NM_001407843.1:c.1642C>G NP_001394772.1:p.Leu548Val missense NM_001407844.1:c.1642C>G NP_001394773.1:p.Leu548Val missense NM_001407845.1:c.1642C>G NP_001394774.1:p.Leu548Val missense NM_001407846.1:c.1642C>G NP_001394775.1:p.Leu548Val missense NM_001407847.1:c.1642C>G NP_001394776.1:p.Leu548Val missense NM_001407848.1:c.1642C>G NP_001394777.1:p.Leu548Val missense NM_001407849.1:c.1642C>G NP_001394778.1:p.Leu548Val missense NM_001407850.1:c.1645C>G NP_001394779.1:p.Leu549Val missense NM_001407851.1:c.1645C>G NP_001394780.1:p.Leu549Val missense NM_001407852.1:c.1645C>G NP_001394781.1:p.Leu549Val missense NM_001407853.1:c.1573C>G NP_001394782.1:p.Leu525Val missense NM_001407854.1:c.1786C>G NP_001394783.1:p.Leu596Val missense NM_001407858.1:c.1786C>G NP_001394787.1:p.Leu596Val missense NM_001407859.1:c.1786C>G NP_001394788.1:p.Leu596Val missense NM_001407860.1:c.1783C>G NP_001394789.1:p.Leu595Val missense NM_001407861.1:c.1783C>G NP_001394790.1:p.Leu595Val missense NM_001407862.1:c.1585C>G NP_001394791.1:p.Leu529Val missense NM_001407863.1:c.1663C>G NP_001394792.1:p.Leu555Val missense NM_001407874.1:c.1582C>G NP_001394803.1:p.Leu528Val missense NM_001407875.1:c.1582C>G NP_001394804.1:p.Leu528Val missense NM_001407879.1:c.1576C>G NP_001394808.1:p.Leu526Val missense NM_001407881.1:c.1576C>G NP_001394810.1:p.Leu526Val missense NM_001407882.1:c.1576C>G NP_001394811.1:p.Leu526Val missense NM_001407884.1:c.1576C>G NP_001394813.1:p.Leu526Val missense NM_001407885.1:c.1576C>G NP_001394814.1:p.Leu526Val missense NM_001407886.1:c.1576C>G NP_001394815.1:p.Leu526Val missense NM_001407887.1:c.1576C>G NP_001394816.1:p.Leu526Val missense NM_001407889.1:c.1576C>G NP_001394818.1:p.Leu526Val missense NM_001407894.1:c.1573C>G NP_001394823.1:p.Leu525Val missense NM_001407895.1:c.1573C>G NP_001394824.1:p.Leu525Val missense NM_001407896.1:c.1573C>G NP_001394825.1:p.Leu525Val missense NM_001407897.1:c.1573C>G NP_001394826.1:p.Leu525Val missense NM_001407898.1:c.1573C>G NP_001394827.1:p.Leu525Val missense NM_001407899.1:c.1573C>G NP_001394828.1:p.Leu525Val missense NM_001407900.1:c.1576C>G NP_001394829.1:p.Leu526Val missense NM_001407902.1:c.1576C>G NP_001394831.1:p.Leu526Val missense NM_001407904.1:c.1576C>G NP_001394833.1:p.Leu526Val missense NM_001407906.1:c.1576C>G NP_001394835.1:p.Leu526Val missense NM_001407907.1:c.1576C>G NP_001394836.1:p.Leu526Val missense NM_001407908.1:c.1576C>G NP_001394837.1:p.Leu526Val missense NM_001407909.1:c.1576C>G NP_001394838.1:p.Leu526Val missense NM_001407910.1:c.1576C>G NP_001394839.1:p.Leu526Val missense NM_001407915.1:c.1573C>G NP_001394844.1:p.Leu525Val missense NM_001407916.1:c.1573C>G NP_001394845.1:p.Leu525Val missense NM_001407917.1:c.1573C>G NP_001394846.1:p.Leu525Val missense NM_001407918.1:c.1573C>G NP_001394847.1:p.Leu525Val missense NM_001407919.1:c.1663C>G NP_001394848.1:p.Leu555Val missense NM_001407920.1:c.1522C>G NP_001394849.1:p.Leu508Val missense NM_001407921.1:c.1522C>G NP_001394850.1:p.Leu508Val missense NM_001407922.1:c.1522C>G NP_001394851.1:p.Leu508Val missense NM_001407923.1:c.1522C>G NP_001394852.1:p.Leu508Val missense NM_001407924.1:c.1522C>G NP_001394853.1:p.Leu508Val missense NM_001407925.1:c.1522C>G NP_001394854.1:p.Leu508Val missense NM_001407926.1:c.1522C>G NP_001394855.1:p.Leu508Val missense NM_001407927.1:c.1522C>G NP_001394856.1:p.Leu508Val missense NM_001407928.1:c.1522C>G NP_001394857.1:p.Leu508Val missense NM_001407929.1:c.1522C>G NP_001394858.1:p.Leu508Val missense NM_001407930.1:c.1519C>G NP_001394859.1:p.Leu507Val missense NM_001407931.1:c.1519C>G NP_001394860.1:p.Leu507Val missense NM_001407932.1:c.1519C>G NP_001394861.1:p.Leu507Val missense NM_001407933.1:c.1522C>G NP_001394862.1:p.Leu508Val missense NM_001407934.1:c.1519C>G NP_001394863.1:p.Leu507Val missense NM_001407935.1:c.1522C>G NP_001394864.1:p.Leu508Val missense NM_001407936.1:c.1519C>G NP_001394865.1:p.Leu507Val missense NM_001407937.1:c.1663C>G NP_001394866.1:p.Leu555Val missense NM_001407938.1:c.1663C>G NP_001394867.1:p.Leu555Val missense NM_001407939.1:c.1663C>G NP_001394868.1:p.Leu555Val missense NM_001407940.1:c.1660C>G NP_001394869.1:p.Leu554Val missense NM_001407941.1:c.1660C>G NP_001394870.1:p.Leu554Val missense NM_001407942.1:c.1645C>G NP_001394871.1:p.Leu549Val missense NM_001407943.1:c.1642C>G NP_001394872.1:p.Leu548Val missense NM_001407944.1:c.1645C>G NP_001394873.1:p.Leu549Val missense NM_001407945.1:c.1645C>G NP_001394874.1:p.Leu549Val missense NM_001407946.1:c.1453C>G NP_001394875.1:p.Leu485Val missense NM_001407947.1:c.1453C>G NP_001394876.1:p.Leu485Val missense NM_001407948.1:c.1453C>G NP_001394877.1:p.Leu485Val missense NM_001407949.1:c.1453C>G NP_001394878.1:p.Leu485Val missense NM_001407950.1:c.1453C>G NP_001394879.1:p.Leu485Val missense NM_001407951.1:c.1453C>G NP_001394880.1:p.Leu485Val missense NM_001407952.1:c.1453C>G NP_001394881.1:p.Leu485Val missense NM_001407953.1:c.1453C>G NP_001394882.1:p.Leu485Val missense NM_001407954.1:c.1450C>G NP_001394883.1:p.Leu484Val missense NM_001407955.1:c.1450C>G NP_001394884.1:p.Leu484Val missense NM_001407956.1:c.1450C>G NP_001394885.1:p.Leu484Val missense NM_001407957.1:c.1453C>G NP_001394886.1:p.Leu485Val missense NM_001407958.1:c.1450C>G NP_001394887.1:p.Leu484Val missense NM_001407959.1:c.1405C>G NP_001394888.1:p.Leu469Val missense NM_001407960.1:c.1405C>G NP_001394889.1:p.Leu469Val missense NM_001407962.1:c.1402C>G NP_001394891.1:p.Leu468Val missense NM_001407963.1:c.1405C>G NP_001394892.1:p.Leu469Val missense NM_001407964.1:c.1642C>G NP_001394893.1:p.Leu548Val missense NM_001407965.1:c.1282C>G NP_001394894.1:p.Leu428Val missense NM_001407966.1:c.898C>G NP_001394895.1:p.Leu300Val missense NM_001407967.1:c.898C>G NP_001394896.1:p.Leu300Val missense NM_001407968.1:c.787+999C>G intron variant NM_001407969.1:c.787+999C>G intron variant NM_001407970.1:c.787+999C>G intron variant NM_001407971.1:c.787+999C>G intron variant NM_001407972.1:c.784+999C>G intron variant NM_001407973.1:c.787+999C>G intron variant NM_001407974.1:c.787+999C>G intron variant NM_001407975.1:c.787+999C>G intron variant NM_001407976.1:c.787+999C>G intron variant NM_001407977.1:c.787+999C>G intron variant NM_001407978.1:c.787+999C>G intron variant NM_001407979.1:c.787+999C>G intron variant NM_001407980.1:c.787+999C>G intron variant NM_001407981.1:c.787+999C>G intron variant NM_001407982.1:c.787+999C>G intron variant NM_001407983.1:c.787+999C>G intron variant NM_001407984.1:c.784+999C>G intron variant NM_001407985.1:c.784+999C>G intron variant NM_001407986.1:c.784+999C>G intron variant NM_001407990.1:c.787+999C>G intron variant NM_001407991.1:c.784+999C>G intron variant NM_001407992.1:c.784+999C>G intron variant NM_001407993.1:c.787+999C>G intron variant NM_001408392.1:c.784+999C>G intron variant NM_001408396.1:c.784+999C>G intron variant NM_001408397.1:c.784+999C>G intron variant NM_001408398.1:c.784+999C>G intron variant NM_001408399.1:c.784+999C>G intron variant NM_001408400.1:c.784+999C>G intron variant NM_001408401.1:c.784+999C>G intron variant NM_001408402.1:c.784+999C>G intron variant NM_001408403.1:c.787+999C>G intron variant NM_001408404.1:c.787+999C>G intron variant NM_001408406.1:c.790+996C>G intron variant NM_001408407.1:c.784+999C>G intron variant NM_001408408.1:c.778+999C>G intron variant NM_001408409.1:c.709+999C>G intron variant NM_001408410.1:c.646+999C>G intron variant NM_001408411.1:c.709+999C>G intron variant NM_001408412.1:c.709+999C>G intron variant NM_001408413.1:c.706+999C>G intron variant NM_001408414.1:c.709+999C>G intron variant NM_001408415.1:c.709+999C>G intron variant NM_001408416.1:c.706+999C>G intron variant NM_001408418.1:c.670+2101C>G intron variant NM_001408419.1:c.670+2101C>G intron variant NM_001408420.1:c.670+2101C>G intron variant NM_001408421.1:c.667+2101C>G intron variant NM_001408422.1:c.670+2101C>G intron variant NM_001408423.1:c.670+2101C>G intron variant NM_001408424.1:c.667+2101C>G intron variant NM_001408425.1:c.664+999C>G intron variant NM_001408426.1:c.664+999C>G intron variant NM_001408427.1:c.664+999C>G intron variant NM_001408428.1:c.664+999C>G intron variant NM_001408429.1:c.664+999C>G intron variant NM_001408430.1:c.664+999C>G intron variant NM_001408431.1:c.667+2101C>G intron variant NM_001408432.1:c.661+999C>G intron variant NM_001408433.1:c.661+999C>G intron variant NM_001408434.1:c.661+999C>G intron variant NM_001408435.1:c.661+999C>G intron variant NM_001408436.1:c.664+999C>G intron variant NM_001408437.1:c.664+999C>G intron variant NM_001408438.1:c.664+999C>G intron variant NM_001408439.1:c.664+999C>G intron variant NM_001408440.1:c.664+999C>G intron variant NM_001408441.1:c.664+999C>G intron variant NM_001408442.1:c.664+999C>G intron variant NM_001408443.1:c.664+999C>G intron variant NM_001408444.1:c.664+999C>G intron variant NM_001408445.1:c.661+999C>G intron variant NM_001408446.1:c.661+999C>G intron variant NM_001408447.1:c.661+999C>G intron variant NM_001408448.1:c.661+999C>G intron variant NM_001408450.1:c.661+999C>G intron variant NM_001408451.1:c.652+999C>G intron variant NM_001408452.1:c.646+999C>G intron variant NM_001408453.1:c.646+999C>G intron variant NM_001408454.1:c.646+999C>G intron variant NM_001408455.1:c.646+999C>G intron variant NM_001408456.1:c.646+999C>G intron variant NM_001408457.1:c.646+999C>G intron variant NM_001408458.1:c.646+999C>G intron variant NM_001408459.1:c.646+999C>G intron variant NM_001408460.1:c.646+999C>G intron variant NM_001408461.1:c.646+999C>G intron variant NM_001408462.1:c.643+999C>G intron variant NM_001408463.1:c.643+999C>G intron variant NM_001408464.1:c.643+999C>G intron variant NM_001408465.1:c.643+999C>G intron variant NM_001408466.1:c.646+999C>G intron variant NM_001408467.1:c.646+999C>G intron variant NM_001408468.1:c.643+999C>G intron variant NM_001408469.1:c.646+999C>G intron variant NM_001408470.1:c.643+999C>G intron variant NM_001408472.1:c.787+999C>G intron variant NM_001408473.1:c.784+999C>G intron variant NM_001408474.1:c.586+999C>G intron variant NM_001408475.1:c.583+999C>G intron variant NM_001408476.1:c.586+999C>G intron variant NM_001408478.1:c.577+999C>G intron variant NM_001408479.1:c.577+999C>G intron variant NM_001408480.1:c.577+999C>G intron variant NM_001408481.1:c.577+999C>G intron variant NM_001408482.1:c.577+999C>G intron variant NM_001408483.1:c.577+999C>G intron variant NM_001408484.1:c.577+999C>G intron variant NM_001408485.1:c.577+999C>G intron variant NM_001408489.1:c.577+999C>G intron variant NM_001408490.1:c.574+999C>G intron variant NM_001408491.1:c.574+999C>G intron variant NM_001408492.1:c.577+999C>G intron variant NM_001408493.1:c.574+999C>G intron variant NM_001408494.1:c.548-2713C>G intron variant NM_001408495.1:c.545-2713C>G intron variant NM_001408496.1:c.523+999C>G intron variant NM_001408497.1:c.523+999C>G intron variant NM_001408498.1:c.523+999C>G intron variant NM_001408499.1:c.523+999C>G intron variant NM_001408500.1:c.523+999C>G intron variant NM_001408501.1:c.523+999C>G intron variant NM_001408502.1:c.454+999C>G intron variant NM_001408503.1:c.520+999C>G intron variant NM_001408504.1:c.520+999C>G intron variant NM_001408505.1:c.520+999C>G intron variant NM_001408506.1:c.460+2101C>G intron variant NM_001408507.1:c.460+2101C>G intron variant NM_001408508.1:c.451+999C>G intron variant NM_001408509.1:c.451+999C>G intron variant NM_001408510.1:c.406+999C>G intron variant NM_001408511.1:c.404-2713C>G intron variant NM_001408512.1:c.283+999C>G intron variant NM_001408513.1:c.577+999C>G intron variant NM_001408514.1:c.577+999C>G intron variant NM_007297.4:c.1645C>G NP_009228.2:p.Leu549Val missense NM_007298.4:c.787+999C>G intron variant NM_007299.4:c.787+999C>G intron variant NM_007300.4:c.1786C>G NP_009231.2:p.Leu596Val missense NR_027676.1:n.1922C>G NC_000017.11:g.43093745G>C NC_000017.10:g.41245762G>C NG_005905.2:g.124239C>G LRG_292:g.124239C>G LRG_292t1:c.1786C>G LRG_292p1:p.Leu596Val U14680.1:n.1905C>G - Protein change
- L596V, L549V, L428V, L525V, L555V, L570V, L300V, L468V, L484V, L485V, L526V, L593V, L469V, L508V, L529V, L554V, L569V, L595V, L507V, L528V, L548V
- Other names
- -
- Canonical SPDI
- NC_000017.11:43093744:G:C
-
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.
-
0.00040 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 | ||
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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 |
13037 | 14843 |
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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Uncertain significance (2) |
criteria provided, single submitter
|
Oct 2, 2023 | RCV000111683.5 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
May 22, 2023 | RCV001013178.13 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 24, 2024 | RCV001368144.8 | |
Uncertain significance (1) |
criteria provided, single submitter
|
May 2, 2022 | RCV002265583.1 |
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
(May 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002548449.1
First in ClinVar: Jul 18, 2022 Last updated: Jul 18, 2022 |
Comment:
Variant summary: BRCA1 c.1786C>G (p.Leu596Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign … (more)
Variant summary: BRCA1 c.1786C>G (p.Leu596Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251094 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1786C>G has been reported in the literature in individual(s) affected with Hereditary Breast And Ovarian Cancer Syndrome (Judkins_2005). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The variant was analyzed via multifactorial analysis which concluded there was insufficient data to assign an IARC classification (Parsons_2019). Three ClinVar submitters have assessed the variant since 2014: all have classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
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Uncertain Significance
(Oct 02, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
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: SCV004818283.1
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 leucine with valine at codon 596 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces leucine with valine at codon 596 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a multifactorial analysis that provided likelihood ratios on tumor pathology, segregation and family history of 0.4, 0.9986 and 1.2796, respectively (PMID: 31131967). This variant has been identified in 2/251094 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: 3
|
|
Uncertain significance
(May 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001173728.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.L596V variant (also known as c.1786C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide … (more)
The p.L596V variant (also known as c.1786C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 1786. The leucine at codon 596 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not 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)
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Likely benign
(Mar 23, 2023)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003849735.1
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).
|
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Uncertain significance
(Jan 24, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001564526.4
First in ClinVar: Apr 13, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 596 of the BRCA1 protein (p.Leu596Val). … (more)
This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 596 of the BRCA1 protein (p.Leu596Val). This variant is present in population databases (rs80357371, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 54347). 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 with a negative predictive value of 95%. 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)
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Uncertain significance
(Apr 27, 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: SCV001354710.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces leucine with valine at codon 596 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces leucine with valine at codon 596 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). To our knowledge, functional studies have not been reported for this variant. A multifactorial analysis reported likelihood ratios for pathogenicity based on on tumor pathology, segregation and family history of 0.4, 0.9986 and 1.2796, respectively (PMID: 31131967). This variant has been identified in 2/251094 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
(Nov 25, 2004)
|
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: SCV000144183.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
|
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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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 |
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
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 rs80357371 ...
HelpRecord 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.