ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.736T>G (p.Leu246Val)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.736T>G (p.Leu246Val)
Variation ID: 41835 Accession: VCV000041835.98
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43094795 (GRCh38) [ NCBI UCSC ] 17: 41246812 (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 12, 2013 Aug 4, 2024 Aug 10, 2015 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.736T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu246Val missense NM_001407571.1:c.523T>G NP_001394500.1:p.Leu175Val missense NM_001407581.1:c.736T>G NP_001394510.1:p.Leu246Val missense NM_001407582.1:c.736T>G NP_001394511.1:p.Leu246Val missense NM_001407583.1:c.736T>G NP_001394512.1:p.Leu246Val missense NM_001407585.1:c.736T>G NP_001394514.1:p.Leu246Val missense NM_001407587.1:c.733T>G NP_001394516.1:p.Leu245Val missense NM_001407590.1:c.733T>G NP_001394519.1:p.Leu245Val missense NM_001407591.1:c.733T>G NP_001394520.1:p.Leu245Val missense NM_001407593.1:c.736T>G NP_001394522.1:p.Leu246Val missense NM_001407594.1:c.736T>G NP_001394523.1:p.Leu246Val missense NM_001407596.1:c.736T>G NP_001394525.1:p.Leu246Val missense NM_001407597.1:c.736T>G NP_001394526.1:p.Leu246Val missense NM_001407598.1:c.736T>G NP_001394527.1:p.Leu246Val missense NM_001407602.1:c.736T>G NP_001394531.1:p.Leu246Val missense NM_001407603.1:c.736T>G NP_001394532.1:p.Leu246Val missense NM_001407605.1:c.736T>G NP_001394534.1:p.Leu246Val missense NM_001407610.1:c.733T>G NP_001394539.1:p.Leu245Val missense NM_001407611.1:c.733T>G NP_001394540.1:p.Leu245Val missense NM_001407612.1:c.733T>G NP_001394541.1:p.Leu245Val missense NM_001407613.1:c.733T>G NP_001394542.1:p.Leu245Val missense NM_001407614.1:c.733T>G NP_001394543.1:p.Leu245Val missense NM_001407615.1:c.733T>G NP_001394544.1:p.Leu245Val missense NM_001407616.1:c.736T>G NP_001394545.1:p.Leu246Val missense NM_001407617.1:c.736T>G NP_001394546.1:p.Leu246Val missense NM_001407618.1:c.736T>G NP_001394547.1:p.Leu246Val missense NM_001407619.1:c.736T>G NP_001394548.1:p.Leu246Val missense NM_001407620.1:c.736T>G NP_001394549.1:p.Leu246Val missense NM_001407621.1:c.736T>G NP_001394550.1:p.Leu246Val missense NM_001407622.1:c.736T>G NP_001394551.1:p.Leu246Val missense NM_001407623.1:c.736T>G NP_001394552.1:p.Leu246Val missense NM_001407624.1:c.736T>G NP_001394553.1:p.Leu246Val missense NM_001407625.1:c.736T>G NP_001394554.1:p.Leu246Val missense NM_001407626.1:c.736T>G NP_001394555.1:p.Leu246Val missense NM_001407627.1:c.733T>G NP_001394556.1:p.Leu245Val missense NM_001407628.1:c.733T>G NP_001394557.1:p.Leu245Val missense NM_001407629.1:c.733T>G NP_001394558.1:p.Leu245Val missense NM_001407630.1:c.733T>G NP_001394559.1:p.Leu245Val missense NM_001407631.1:c.733T>G NP_001394560.1:p.Leu245Val missense NM_001407632.1:c.733T>G NP_001394561.1:p.Leu245Val missense NM_001407633.1:c.733T>G NP_001394562.1:p.Leu245Val missense NM_001407634.1:c.733T>G NP_001394563.1:p.Leu245Val missense NM_001407635.1:c.733T>G NP_001394564.1:p.Leu245Val missense NM_001407636.1:c.733T>G NP_001394565.1:p.Leu245Val missense NM_001407637.1:c.733T>G NP_001394566.1:p.Leu245Val missense NM_001407638.1:c.733T>G NP_001394567.1:p.Leu245Val missense NM_001407639.1:c.736T>G NP_001394568.1:p.Leu246Val missense NM_001407640.1:c.736T>G NP_001394569.1:p.Leu246Val missense NM_001407641.1:c.736T>G NP_001394570.1:p.Leu246Val missense NM_001407642.1:c.736T>G NP_001394571.1:p.Leu246Val missense NM_001407644.1:c.733T>G NP_001394573.1:p.Leu245Val missense NM_001407645.1:c.733T>G NP_001394574.1:p.Leu245Val missense NM_001407646.1:c.727T>G NP_001394575.1:p.Leu243Val missense NM_001407647.1:c.727T>G NP_001394576.1:p.Leu243Val missense NM_001407648.1:c.613T>G NP_001394577.1:p.Leu205Val missense NM_001407649.1:c.610T>G NP_001394578.1:p.Leu204Val missense NM_001407652.1:c.736T>G NP_001394581.1:p.Leu246Val missense NM_001407653.1:c.658T>G NP_001394582.1:p.Leu220Val missense NM_001407654.1:c.658T>G NP_001394583.1:p.Leu220Val missense NM_001407655.1:c.658T>G NP_001394584.1:p.Leu220Val missense NM_001407656.1:c.658T>G NP_001394585.1:p.Leu220Val missense NM_001407657.1:c.658T>G NP_001394586.1:p.Leu220Val missense NM_001407658.1:c.658T>G NP_001394587.1:p.Leu220Val missense NM_001407659.1:c.655T>G NP_001394588.1:p.Leu219Val missense NM_001407660.1:c.655T>G NP_001394589.1:p.Leu219Val missense NM_001407661.1:c.655T>G NP_001394590.1:p.Leu219Val missense NM_001407662.1:c.655T>G NP_001394591.1:p.Leu219Val missense NM_001407663.1:c.658T>G NP_001394592.1:p.Leu220Val missense NM_001407664.1:c.613T>G NP_001394593.1:p.Leu205Val missense NM_001407665.1:c.613T>G NP_001394594.1:p.Leu205Val missense NM_001407666.1:c.613T>G NP_001394595.1:p.Leu205Val missense NM_001407667.1:c.613T>G NP_001394596.1:p.Leu205Val missense NM_001407668.1:c.613T>G NP_001394597.1:p.Leu205Val missense NM_001407669.1:c.613T>G NP_001394598.1:p.Leu205Val missense NM_001407670.1:c.610T>G NP_001394599.1:p.Leu204Val missense NM_001407671.1:c.610T>G NP_001394600.1:p.Leu204Val missense NM_001407672.1:c.610T>G NP_001394601.1:p.Leu204Val missense NM_001407673.1:c.610T>G NP_001394602.1:p.Leu204Val missense NM_001407674.1:c.613T>G NP_001394603.1:p.Leu205Val missense NM_001407675.1:c.613T>G NP_001394604.1:p.Leu205Val missense NM_001407676.1:c.613T>G NP_001394605.1:p.Leu205Val missense NM_001407677.1:c.613T>G NP_001394606.1:p.Leu205Val missense NM_001407678.1:c.613T>G NP_001394607.1:p.Leu205Val missense NM_001407679.1:c.613T>G NP_001394608.1:p.Leu205Val missense NM_001407680.1:c.613T>G NP_001394609.1:p.Leu205Val missense NM_001407681.1:c.613T>G NP_001394610.1:p.Leu205Val missense NM_001407682.1:c.613T>G NP_001394611.1:p.Leu205Val missense NM_001407683.1:c.613T>G NP_001394612.1:p.Leu205Val missense NM_001407684.1:c.736T>G NP_001394613.1:p.Leu246Val missense NM_001407685.1:c.610T>G NP_001394614.1:p.Leu204Val missense NM_001407686.1:c.610T>G NP_001394615.1:p.Leu204Val missense NM_001407687.1:c.610T>G NP_001394616.1:p.Leu204Val missense NM_001407688.1:c.610T>G NP_001394617.1:p.Leu204Val missense NM_001407689.1:c.610T>G NP_001394618.1:p.Leu204Val missense NM_001407690.1:c.610T>G NP_001394619.1:p.Leu204Val missense NM_001407691.1:c.610T>G NP_001394620.1:p.Leu204Val missense NM_001407692.1:c.595T>G NP_001394621.1:p.Leu199Val missense NM_001407694.1:c.595T>G NP_001394623.1:p.Leu199Val missense NM_001407695.1:c.595T>G NP_001394624.1:p.Leu199Val missense NM_001407696.1:c.595T>G NP_001394625.1:p.Leu199Val missense NM_001407697.1:c.595T>G NP_001394626.1:p.Leu199Val missense NM_001407698.1:c.595T>G NP_001394627.1:p.Leu199Val missense NM_001407724.1:c.595T>G NP_001394653.1:p.Leu199Val missense NM_001407725.1:c.595T>G NP_001394654.1:p.Leu199Val missense NM_001407726.1:c.595T>G NP_001394655.1:p.Leu199Val missense NM_001407727.1:c.595T>G NP_001394656.1:p.Leu199Val missense NM_001407728.1:c.595T>G NP_001394657.1:p.Leu199Val missense NM_001407729.1:c.595T>G NP_001394658.1:p.Leu199Val missense NM_001407730.1:c.595T>G NP_001394659.1:p.Leu199Val missense NM_001407731.1:c.595T>G NP_001394660.1:p.Leu199Val missense NM_001407732.1:c.595T>G NP_001394661.1:p.Leu199Val missense NM_001407733.1:c.595T>G NP_001394662.1:p.Leu199Val missense NM_001407734.1:c.595T>G NP_001394663.1:p.Leu199Val missense NM_001407735.1:c.595T>G NP_001394664.1:p.Leu199Val missense NM_001407736.1:c.595T>G NP_001394665.1:p.Leu199Val missense NM_001407737.1:c.595T>G NP_001394666.1:p.Leu199Val missense NM_001407738.1:c.595T>G NP_001394667.1:p.Leu199Val missense NM_001407739.1:c.595T>G NP_001394668.1:p.Leu199Val missense NM_001407740.1:c.592T>G NP_001394669.1:p.Leu198Val missense NM_001407741.1:c.592T>G NP_001394670.1:p.Leu198Val missense NM_001407742.1:c.592T>G NP_001394671.1:p.Leu198Val missense NM_001407743.1:c.592T>G NP_001394672.1:p.Leu198Val missense NM_001407744.1:c.592T>G NP_001394673.1:p.Leu198Val missense NM_001407745.1:c.592T>G NP_001394674.1:p.Leu198Val missense NM_001407746.1:c.592T>G NP_001394675.1:p.Leu198Val missense NM_001407747.1:c.592T>G NP_001394676.1:p.Leu198Val missense NM_001407748.1:c.592T>G NP_001394677.1:p.Leu198Val missense NM_001407749.1:c.592T>G NP_001394678.1:p.Leu198Val missense NM_001407750.1:c.595T>G NP_001394679.1:p.Leu199Val missense NM_001407751.1:c.595T>G NP_001394680.1:p.Leu199Val missense NM_001407752.1:c.595T>G NP_001394681.1:p.Leu199Val missense NM_001407838.1:c.592T>G NP_001394767.1:p.Leu198Val missense NM_001407839.1:c.592T>G NP_001394768.1:p.Leu198Val missense NM_001407841.1:c.592T>G NP_001394770.1:p.Leu198Val missense NM_001407842.1:c.592T>G NP_001394771.1:p.Leu198Val missense NM_001407843.1:c.592T>G NP_001394772.1:p.Leu198Val missense NM_001407844.1:c.592T>G NP_001394773.1:p.Leu198Val missense NM_001407845.1:c.592T>G NP_001394774.1:p.Leu198Val missense NM_001407846.1:c.592T>G NP_001394775.1:p.Leu198Val missense NM_001407847.1:c.592T>G NP_001394776.1:p.Leu198Val missense NM_001407848.1:c.592T>G NP_001394777.1:p.Leu198Val missense NM_001407849.1:c.592T>G NP_001394778.1:p.Leu198Val missense NM_001407850.1:c.595T>G NP_001394779.1:p.Leu199Val missense NM_001407851.1:c.595T>G NP_001394780.1:p.Leu199Val missense NM_001407852.1:c.595T>G NP_001394781.1:p.Leu199Val missense NM_001407853.1:c.523T>G NP_001394782.1:p.Leu175Val missense NM_001407854.1:c.736T>G NP_001394783.1:p.Leu246Val missense NM_001407858.1:c.736T>G NP_001394787.1:p.Leu246Val missense NM_001407859.1:c.736T>G NP_001394788.1:p.Leu246Val missense NM_001407860.1:c.733T>G NP_001394789.1:p.Leu245Val missense NM_001407861.1:c.733T>G NP_001394790.1:p.Leu245Val missense NM_001407862.1:c.535T>G NP_001394791.1:p.Leu179Val missense NM_001407863.1:c.613T>G NP_001394792.1:p.Leu205Val missense NM_001407874.1:c.532T>G NP_001394803.1:p.Leu178Val missense NM_001407875.1:c.532T>G NP_001394804.1:p.Leu178Val missense NM_001407879.1:c.526T>G NP_001394808.1:p.Leu176Val missense NM_001407881.1:c.526T>G NP_001394810.1:p.Leu176Val missense NM_001407882.1:c.526T>G NP_001394811.1:p.Leu176Val missense NM_001407884.1:c.526T>G NP_001394813.1:p.Leu176Val missense NM_001407885.1:c.526T>G NP_001394814.1:p.Leu176Val missense NM_001407886.1:c.526T>G NP_001394815.1:p.Leu176Val missense NM_001407887.1:c.526T>G NP_001394816.1:p.Leu176Val missense NM_001407889.1:c.526T>G NP_001394818.1:p.Leu176Val missense NM_001407894.1:c.523T>G NP_001394823.1:p.Leu175Val missense NM_001407895.1:c.523T>G NP_001394824.1:p.Leu175Val missense NM_001407896.1:c.523T>G NP_001394825.1:p.Leu175Val missense NM_001407897.1:c.523T>G NP_001394826.1:p.Leu175Val missense NM_001407898.1:c.523T>G NP_001394827.1:p.Leu175Val missense NM_001407899.1:c.523T>G NP_001394828.1:p.Leu175Val missense NM_001407900.1:c.526T>G NP_001394829.1:p.Leu176Val missense NM_001407902.1:c.526T>G NP_001394831.1:p.Leu176Val missense NM_001407904.1:c.526T>G NP_001394833.1:p.Leu176Val missense NM_001407906.1:c.526T>G NP_001394835.1:p.Leu176Val missense NM_001407907.1:c.526T>G NP_001394836.1:p.Leu176Val missense NM_001407908.1:c.526T>G NP_001394837.1:p.Leu176Val missense NM_001407909.1:c.526T>G NP_001394838.1:p.Leu176Val missense NM_001407910.1:c.526T>G NP_001394839.1:p.Leu176Val missense NM_001407915.1:c.523T>G NP_001394844.1:p.Leu175Val missense NM_001407916.1:c.523T>G NP_001394845.1:p.Leu175Val missense NM_001407917.1:c.523T>G NP_001394846.1:p.Leu175Val missense NM_001407918.1:c.523T>G NP_001394847.1:p.Leu175Val missense NM_001407919.1:c.613T>G NP_001394848.1:p.Leu205Val missense NM_001407920.1:c.472T>G NP_001394849.1:p.Leu158Val missense NM_001407921.1:c.472T>G NP_001394850.1:p.Leu158Val missense NM_001407922.1:c.472T>G NP_001394851.1:p.Leu158Val missense NM_001407923.1:c.472T>G NP_001394852.1:p.Leu158Val missense NM_001407924.1:c.472T>G NP_001394853.1:p.Leu158Val missense NM_001407925.1:c.472T>G NP_001394854.1:p.Leu158Val missense NM_001407926.1:c.472T>G NP_001394855.1:p.Leu158Val missense NM_001407927.1:c.472T>G NP_001394856.1:p.Leu158Val missense NM_001407928.1:c.472T>G NP_001394857.1:p.Leu158Val missense NM_001407929.1:c.472T>G NP_001394858.1:p.Leu158Val missense NM_001407930.1:c.469T>G NP_001394859.1:p.Leu157Val missense NM_001407931.1:c.469T>G NP_001394860.1:p.Leu157Val missense NM_001407932.1:c.469T>G NP_001394861.1:p.Leu157Val missense NM_001407933.1:c.472T>G NP_001394862.1:p.Leu158Val missense NM_001407934.1:c.469T>G NP_001394863.1:p.Leu157Val missense NM_001407935.1:c.472T>G NP_001394864.1:p.Leu158Val missense NM_001407936.1:c.469T>G NP_001394865.1:p.Leu157Val missense NM_001407937.1:c.613T>G NP_001394866.1:p.Leu205Val missense NM_001407938.1:c.613T>G NP_001394867.1:p.Leu205Val missense NM_001407939.1:c.613T>G NP_001394868.1:p.Leu205Val missense NM_001407940.1:c.610T>G NP_001394869.1:p.Leu204Val missense NM_001407941.1:c.610T>G NP_001394870.1:p.Leu204Val missense NM_001407942.1:c.595T>G NP_001394871.1:p.Leu199Val missense NM_001407943.1:c.592T>G NP_001394872.1:p.Leu198Val missense NM_001407944.1:c.595T>G NP_001394873.1:p.Leu199Val missense NM_001407945.1:c.595T>G NP_001394874.1:p.Leu199Val missense NM_001407946.1:c.403T>G NP_001394875.1:p.Leu135Val missense NM_001407947.1:c.403T>G NP_001394876.1:p.Leu135Val missense NM_001407948.1:c.403T>G NP_001394877.1:p.Leu135Val missense NM_001407949.1:c.403T>G NP_001394878.1:p.Leu135Val missense NM_001407950.1:c.403T>G NP_001394879.1:p.Leu135Val missense NM_001407951.1:c.403T>G NP_001394880.1:p.Leu135Val missense NM_001407952.1:c.403T>G NP_001394881.1:p.Leu135Val missense NM_001407953.1:c.403T>G NP_001394882.1:p.Leu135Val missense NM_001407954.1:c.400T>G NP_001394883.1:p.Leu134Val missense NM_001407955.1:c.400T>G NP_001394884.1:p.Leu134Val missense NM_001407956.1:c.400T>G NP_001394885.1:p.Leu134Val missense NM_001407957.1:c.403T>G NP_001394886.1:p.Leu135Val missense NM_001407958.1:c.400T>G NP_001394887.1:p.Leu134Val missense NM_001407959.1:c.355T>G NP_001394888.1:p.Leu119Val missense NM_001407960.1:c.355T>G NP_001394889.1:p.Leu119Val missense NM_001407962.1:c.352T>G NP_001394891.1:p.Leu118Val missense NM_001407963.1:c.355T>G NP_001394892.1:p.Leu119Val missense NM_001407964.1:c.592T>G NP_001394893.1:p.Leu198Val missense NM_001407965.1:c.232T>G NP_001394894.1:p.Leu78Val missense NM_001407966.1:c.-153T>G NM_001407967.1:c.-153T>G NM_001407968.1:c.736T>G NP_001394897.1:p.Leu246Val missense NM_001407969.1:c.736T>G NP_001394898.1:p.Leu246Val missense NM_001407970.1:c.736T>G NP_001394899.1:p.Leu246Val missense NM_001407971.1:c.736T>G NP_001394900.1:p.Leu246Val missense NM_001407972.1:c.733T>G NP_001394901.1:p.Leu245Val missense NM_001407973.1:c.736T>G NP_001394902.1:p.Leu246Val missense NM_001407974.1:c.736T>G NP_001394903.1:p.Leu246Val missense NM_001407975.1:c.736T>G NP_001394904.1:p.Leu246Val missense NM_001407976.1:c.736T>G NP_001394905.1:p.Leu246Val missense NM_001407977.1:c.736T>G NP_001394906.1:p.Leu246Val missense NM_001407978.1:c.736T>G NP_001394907.1:p.Leu246Val missense NM_001407979.1:c.736T>G NP_001394908.1:p.Leu246Val missense NM_001407980.1:c.736T>G NP_001394909.1:p.Leu246Val missense NM_001407981.1:c.736T>G NP_001394910.1:p.Leu246Val missense NM_001407982.1:c.736T>G NP_001394911.1:p.Leu246Val missense NM_001407983.1:c.736T>G NP_001394912.1:p.Leu246Val missense NM_001407984.1:c.733T>G NP_001394913.1:p.Leu245Val missense NM_001407985.1:c.733T>G NP_001394914.1:p.Leu245Val missense NM_001407986.1:c.733T>G NP_001394915.1:p.Leu245Val missense NM_001407990.1:c.736T>G NP_001394919.1:p.Leu246Val missense NM_001407991.1:c.733T>G NP_001394920.1:p.Leu245Val missense NM_001407992.1:c.733T>G NP_001394921.1:p.Leu245Val missense NM_001407993.1:c.736T>G NP_001394922.1:p.Leu246Val missense NM_001408392.1:c.733T>G NP_001395321.1:p.Leu245Val missense NM_001408396.1:c.733T>G NP_001395325.1:p.Leu245Val missense NM_001408397.1:c.733T>G NP_001395326.1:p.Leu245Val missense NM_001408398.1:c.733T>G NP_001395327.1:p.Leu245Val missense NM_001408399.1:c.733T>G NP_001395328.1:p.Leu245Val missense NM_001408400.1:c.733T>G NP_001395329.1:p.Leu245Val missense NM_001408401.1:c.733T>G NP_001395330.1:p.Leu245Val missense NM_001408402.1:c.733T>G NP_001395331.1:p.Leu245Val missense NM_001408403.1:c.736T>G NP_001395332.1:p.Leu246Val missense NM_001408404.1:c.736T>G NP_001395333.1:p.Leu246Val missense NM_001408406.1:c.736T>G NP_001395335.1:p.Leu246Val missense NM_001408407.1:c.733T>G NP_001395336.1:p.Leu245Val missense NM_001408408.1:c.727T>G NP_001395337.1:p.Leu243Val missense NM_001408409.1:c.658T>G NP_001395338.1:p.Leu220Val missense NM_001408410.1:c.595T>G NP_001395339.1:p.Leu199Val missense NM_001408411.1:c.658T>G NP_001395340.1:p.Leu220Val missense NM_001408412.1:c.658T>G NP_001395341.1:p.Leu220Val missense NM_001408413.1:c.655T>G NP_001395342.1:p.Leu219Val missense NM_001408414.1:c.658T>G NP_001395343.1:p.Leu220Val missense NM_001408415.1:c.658T>G NP_001395344.1:p.Leu220Val missense NM_001408416.1:c.655T>G NP_001395345.1:p.Leu219Val missense NM_001408425.1:c.613T>G NP_001395354.1:p.Leu205Val missense NM_001408426.1:c.613T>G NP_001395355.1:p.Leu205Val missense NM_001408427.1:c.613T>G NP_001395356.1:p.Leu205Val missense NM_001408428.1:c.613T>G NP_001395357.1:p.Leu205Val missense NM_001408429.1:c.613T>G NP_001395358.1:p.Leu205Val missense NM_001408430.1:c.613T>G NP_001395359.1:p.Leu205Val missense NM_001408432.1:c.610T>G NP_001395361.1:p.Leu204Val missense NM_001408433.1:c.610T>G NP_001395362.1:p.Leu204Val missense NM_001408434.1:c.610T>G NP_001395363.1:p.Leu204Val missense NM_001408435.1:c.610T>G NP_001395364.1:p.Leu204Val missense NM_001408436.1:c.613T>G NP_001395365.1:p.Leu205Val missense NM_001408437.1:c.613T>G NP_001395366.1:p.Leu205Val missense NM_001408438.1:c.613T>G NP_001395367.1:p.Leu205Val missense NM_001408439.1:c.613T>G NP_001395368.1:p.Leu205Val missense NM_001408440.1:c.613T>G NP_001395369.1:p.Leu205Val missense NM_001408441.1:c.613T>G NP_001395370.1:p.Leu205Val missense NM_001408442.1:c.613T>G NP_001395371.1:p.Leu205Val missense NM_001408443.1:c.613T>G NP_001395372.1:p.Leu205Val missense NM_001408444.1:c.613T>G NP_001395373.1:p.Leu205Val missense NM_001408445.1:c.610T>G NP_001395374.1:p.Leu204Val missense NM_001408446.1:c.610T>G NP_001395375.1:p.Leu204Val missense NM_001408447.1:c.610T>G NP_001395376.1:p.Leu204Val missense NM_001408448.1:c.610T>G NP_001395377.1:p.Leu204Val missense NM_001408450.1:c.610T>G NP_001395379.1:p.Leu204Val missense NM_001408451.1:c.601T>G NP_001395380.1:p.Leu201Val missense NM_001408452.1:c.595T>G NP_001395381.1:p.Leu199Val missense NM_001408453.1:c.595T>G NP_001395382.1:p.Leu199Val missense NM_001408454.1:c.595T>G NP_001395383.1:p.Leu199Val missense NM_001408455.1:c.595T>G NP_001395384.1:p.Leu199Val missense NM_001408456.1:c.595T>G NP_001395385.1:p.Leu199Val missense NM_001408457.1:c.595T>G NP_001395386.1:p.Leu199Val missense NM_001408458.1:c.595T>G NP_001395387.1:p.Leu199Val missense NM_001408459.1:c.595T>G NP_001395388.1:p.Leu199Val missense NM_001408460.1:c.595T>G NP_001395389.1:p.Leu199Val missense NM_001408461.1:c.595T>G NP_001395390.1:p.Leu199Val missense NM_001408462.1:c.592T>G NP_001395391.1:p.Leu198Val missense NM_001408463.1:c.592T>G NP_001395392.1:p.Leu198Val missense NM_001408464.1:c.592T>G NP_001395393.1:p.Leu198Val missense NM_001408465.1:c.592T>G NP_001395394.1:p.Leu198Val missense NM_001408466.1:c.595T>G NP_001395395.1:p.Leu199Val missense NM_001408467.1:c.595T>G NP_001395396.1:p.Leu199Val missense NM_001408468.1:c.592T>G NP_001395397.1:p.Leu198Val missense NM_001408469.1:c.595T>G NP_001395398.1:p.Leu199Val missense NM_001408470.1:c.592T>G NP_001395399.1:p.Leu198Val missense NM_001408472.1:c.736T>G NP_001395401.1:p.Leu246Val missense NM_001408473.1:c.733T>G NP_001395402.1:p.Leu245Val missense NM_001408474.1:c.535T>G NP_001395403.1:p.Leu179Val missense NM_001408475.1:c.532T>G NP_001395404.1:p.Leu178Val missense NM_001408476.1:c.535T>G NP_001395405.1:p.Leu179Val missense NM_001408478.1:c.526T>G NP_001395407.1:p.Leu176Val missense NM_001408479.1:c.526T>G NP_001395408.1:p.Leu176Val missense NM_001408480.1:c.526T>G NP_001395409.1:p.Leu176Val missense NM_001408481.1:c.526T>G NP_001395410.1:p.Leu176Val missense NM_001408482.1:c.526T>G NP_001395411.1:p.Leu176Val missense NM_001408483.1:c.526T>G NP_001395412.1:p.Leu176Val missense NM_001408484.1:c.526T>G NP_001395413.1:p.Leu176Val missense NM_001408485.1:c.526T>G NP_001395414.1:p.Leu176Val missense NM_001408489.1:c.526T>G NP_001395418.1:p.Leu176Val missense NM_001408490.1:c.523T>G NP_001395419.1:p.Leu175Val missense NM_001408491.1:c.523T>G NP_001395420.1:p.Leu175Val missense NM_001408492.1:c.526T>G NP_001395421.1:p.Leu176Val missense NM_001408493.1:c.523T>G NP_001395422.1:p.Leu175Val missense NM_001408496.1:c.472T>G NP_001395425.1:p.Leu158Val missense NM_001408497.1:c.472T>G NP_001395426.1:p.Leu158Val missense NM_001408498.1:c.472T>G NP_001395427.1:p.Leu158Val missense NM_001408499.1:c.472T>G NP_001395428.1:p.Leu158Val missense NM_001408500.1:c.472T>G NP_001395429.1:p.Leu158Val missense NM_001408501.1:c.472T>G NP_001395430.1:p.Leu158Val missense NM_001408502.1:c.403T>G NP_001395431.1:p.Leu135Val missense NM_001408503.1:c.469T>G NP_001395432.1:p.Leu157Val missense NM_001408504.1:c.469T>G NP_001395433.1:p.Leu157Val missense NM_001408505.1:c.469T>G NP_001395434.1:p.Leu157Val missense NM_001408508.1:c.400T>G NP_001395437.1:p.Leu134Val missense NM_001408509.1:c.400T>G NP_001395438.1:p.Leu134Val missense NM_001408510.1:c.355T>G NP_001395439.1:p.Leu119Val missense NM_001408512.1:c.232T>G NP_001395441.1:p.Leu78Val missense NM_001408513.1:c.526T>G NP_001395442.1:p.Leu176Val missense NM_001408514.1:c.526T>G NP_001395443.1:p.Leu176Val missense NM_007297.4:c.595T>G NP_009228.2:p.Leu199Val missense NM_007298.4:c.736T>G NP_009229.2:p.Leu246Val missense NM_007299.4:c.736T>G NP_009230.2:p.Leu246Val missense NM_007300.4:c.736T>G NP_009231.2:p.Leu246Val missense NM_007304.2:c.736T>G NP_009235.2:p.Leu246Val missense NR_027676.2:n.913T>G non-coding transcript variant NC_000017.11:g.43094795A>C NC_000017.10:g.41246812A>C NG_005905.2:g.123189T>G LRG_292:g.123189T>G LRG_292t1:c.736T>G LRG_292p1:p.Leu246Val P38398:p.Leu246Val U14680.1:n.855T>G - Protein change
- L246V, L199V, L118V, L119V, L134V, L219V, L243V, L176V, L179V, L201V, L204V, L245V, L158V, L175V, L198V, L220V, L135V, L157V, L178V, L205V, L78V
- Other names
- p.L246V:TTG>GTG
- 855T>G
- Canonical SPDI
- NC_000017.11:43094794:A: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.
-
0.00020 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00022
The Genome Aggregation Database (gnomAD), exomes 0.00031
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
The Genome Aggregation Database (gnomAD) 0.00026
Trans-Omics for Precision Medicine (TOPMed) 0.00028
1000 Genomes Project 30x 0.00031
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 |
13021 | 14825 |
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. |
---|---|---|---|---|
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2023 | RCV000034762.43 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000049113.26 | |
Likely benign (4) |
criteria provided, single submitter
|
Nov 15, 2022 | RCV000148400.15 | |
Benign (10) |
reviewed by expert panel
|
Aug 10, 2015 | RCV000112779.26 | |
Conflicting interpretations of pathogenicity (8) |
criteria provided, conflicting classifications
|
Aug 15, 2023 | RCV000157724.33 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 15, 2021 | RCV000162555.14 | |
Likely benign (1) |
criteria provided, single submitter
|
Mar 22, 2022 | RCV002504870.8 | |
Benign (1) |
no assertion criteria provided
|
- | RCV001353473.10 |
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. |
|
---|---|---|---|---|---|
Benign
(Aug 10, 2015)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000244410.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on … (more)
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000000531 (less)
|
|
Benign
(Nov 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000195886.1
First in ClinVar: May 06, 2016 Last updated: May 06, 2016 |
Tissue: Blood
|
|
Uncertain significance
(Jan 24, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000538445.1
First in ClinVar: Feb 24, 2015 Last updated: Feb 24, 2015 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has been reported in HGMD in 1 individual, showing that it leads to loss of expression of BRCA1. This variant is present in ExAC with a Max MAF of 0.04% (25/65600 chrs). It is classified in ClinVar with 3 stars as benign by 5 submitters (including expert panel ENIGMA), Likely benign by 3 submitters, and VUS by 3 submitters. (less)
Method: Genome/Exome Filtration
|
|
Likely benign
(Jul 15, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000593663.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
|
|
Benign
(Nov 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000167234.11
First in ClinVar: Jun 23, 2014 Last updated: Aug 27, 2017 |
Comment:
This variant is associated with the following publications: (PMID: 27153395, 22703879, 24055113, 19200354, 23867111, 21520273, 25637381, 21990134, 25782689, 15235020, 16014699, 21965345, 15307796, 15300854, 25823446, 26246475, … (more)
This variant is associated with the following publications: (PMID: 27153395, 22703879, 24055113, 19200354, 23867111, 21520273, 25637381, 21990134, 25782689, 15235020, 16014699, 21965345, 15307796, 15300854, 25823446, 26246475, 26332594, 33087888) (less)
|
|
Benign
(Jan 13, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683352.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
Likely benign
(Nov 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV000324818.2
First in ClinVar: Jul 01, 2016 Last updated: Feb 04, 2024 |
|
|
Benign
(Mar 31, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602736.6
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
|
|
Benign
(Feb 05, 2024)
|
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: SCV004818415.1
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)
|
Number of individuals with the variant: 88
|
|
Benign
(Nov 18, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000212965.6
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Likely benign
(Apr 25, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000267857.1
First in ClinVar: Jan 31, 2016 Last updated: Jan 31, 2016 |
|
|
Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001140623.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
Uncertain significance
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001280988.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Likely benign
(Mar 15, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002537895.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Likely benign
(Jun 08, 2014)
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criteria provided, single submitter
Method: literature only
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Breast-ovarian cancer, familial 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220389.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Likely benign
(Mar 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002808838.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely benign
(Jun 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333444.2
First in ClinVar: May 31, 2020 Last updated: Mar 11, 2023 |
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Benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551042.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000077126.16
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
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Likely benign
(Jul 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001501183.21
First in ClinVar: Mar 14, 2021 Last updated: Aug 04, 2024 |
Comment:
BRCA1: BP1, BS3:Supporting
Number of individuals with the variant: 4
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variant of unknown significance
(Jul 13, 2012)
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no assertion criteria provided
Method: research
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not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043184.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Uncertain significance.
Number of individuals with the variant: 2
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799917.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001905687.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931498.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Uncertain significance
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145673.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 18
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Central/Eastern European
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Netherlands
Observation 4:
Number of individuals with the variant: 1
Geographic origin: English
Observation 5:
Number of individuals with the variant: 3
Geographic origin: Western European
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: African American
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Austrian
Geographic origin: Austria
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Spain
Observation 9:
Number of individuals with the variant: 3
Ethnicity/Population group: Central/Eastern European
Observation 10:
Number of individuals with the variant: 44
Ethnicity/Population group: Western European
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central/Eastern European
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, French
Observation 13:
Number of individuals with the variant: 3
Ethnicity/Population group: Western European, French Canadian
Observation 14:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Native American
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Uncertain significance
(Jun 01, 2014)
|
no assertion criteria provided
Method: research
|
Breast and/or ovarian cancer
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190099.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
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Uncertain significance
(Jun 04, 2015)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: no
Allele origin:
germline
|
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Study: CSER-NextGen
Accession: SCV000493711.1 First in ClinVar: Jan 23, 2017 Last updated: Jan 23, 2017 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733666.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Likely benign
(Apr 03, 2017)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000778774.1
First in ClinVar: Feb 24, 2015 Last updated: Feb 24, 2015 |
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Likely benign
(Oct 25, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000787913.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Uncertain significance
(Mar 15, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863627.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591299.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA1, p.Leu246Val variant was identified in 7 of 7716 proband chromosomes (frequency: 0.001) from individuals or families with breast and ovarian cancer (Akbari 2011, … (more)
The BRCA1, p.Leu246Val variant was identified in 7 of 7716 proband chromosomes (frequency: 0.001) from individuals or families with breast and ovarian cancer (Akbari 2011, Capanu 2011, Diez 2003). The variant was also identified in dbSNP (ID: rs28897675) “With Uncertain significance allele”, with a minor allele frequency of 0.0002 (1000 Genomes Project), NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, LOVD, the ClinVar database (classified as a benign variant by the Invitae, GeneDx and Ambry genetics; classified as Likely benign by Counsyl; classified as Uncertain significance by BIC, by Biesecker Laboratory and by CSER_CC_NCGL), GeneInsight COGR database (1X, classified as “Benign” by a clinical laboratory), the BIC database (80X with unknown clinical importance), and UMD (17X as a neutral variant). In UMD the variant was identified with a co-occurring pathogenic BRCA1 and BRCA2 variants (BRCA1 c.3901_3902delAG (p.Ser1301X); BRCA2 c.5984dup (p.Asn1995delinsLys)), increasing the likelihood that the p.Leu246Val variant does not have clinical significance. This variant was identified in the 1000 Genomes Project in 1 of 5000 chromosomes (frequency: 0.0002), Exome Variant Server project in 3 of 8600 European American alleles, the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 26 of 76950 chromosomes (frequency: 0.0003) from a population of European (Non-Finnish) and Latino individuals, increasing the likelihood this could be a low frequency benign variant. The p.Leu246 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In addition, the Val residue is also present in opossum, which would increase the likelihood this variant may not have functional significance. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. RNA based analysis by Sharp (2004) suggest that the mutation is associated with either constitutive skipping of exon 11, or monoallelic BRCA1 expression. However, two functional studies characterized the variant as neutral (Abkevich 2004, Gómez García 2009). In addition, this variant have been observed with two or more known deleterious mutations, increasing the likelihood this variant does not have clinical significance (Tavtigian 2006, Judkins 2005). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. (less)
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953037.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972436.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Benign
(Mar 02, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV004244149.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
A high-throughput functional complementation assay for classification of BRCA1 missense variants. | Bouwman P | Cancer discovery | 2013 | PMID: 23867111 |
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). | Lindor NM | Human mutation | 2012 | PMID: 21990134 |
Clinical impact of unclassified variants of the BRCA1 and BRCA2 genes. | Akbari MR | Journal of medical genetics | 2011 | PMID: 21965345 |
Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling. | Capanu M | Genetic epidemiology | 2011 | PMID: 21520273 |
Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer. | Cavallone L | Familial cancer | 2010 | PMID: 20694749 |
Selecting for BRCA1 testing using a combination of homogeneous selection criteria and immunohistochemical characteristics of breast cancers. | Miolo G | BMC cancer | 2009 | PMID: 19818148 |
A method to assess the clinical significance of unclassified variants in the BRCA1 and BRCA2 genes based on cancer family history. | Gómez García EB | Breast cancer research : BCR | 2009 | PMID: 19200354 |
Incorporating the amino acid properties to predict the significance of missense mutations. | Lee TC | Amino acids | 2008 | PMID: 18415037 |
Classification of missense variants of unknown significance in BRCA1 based on clinical and tumor information. | Osorio A | Human mutation | 2007 | PMID: 17279547 |
Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. | Tavtigian SV | Journal of medical genetics | 2006 | PMID: 16014699 |
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 |
A high-throughput mutation detection method based on heteroduplex analysis using graft copolymer matrixes: application to Brca1 and Brca2 analysis. | Weber J | Analytical chemistry | 2004 | PMID: 15307796 |
RNA analysis reveals splicing mutations and loss of expression defects in MLH1 and BRCA1. | Sharp A | Human mutation | 2004 | PMID: 15300854 |
Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. | Abkevich V | Journal of medical genetics | 2004 | PMID: 15235020 |
Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. | Díez O | Human mutation | 2003 | PMID: 12955716 |
http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA1&action=search_all&search_Variant%2FDNA=c.736T%3EG | - | - | - | - |
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Text-mined citations for rs28897675 ...
HelpRecord last updated Sep 17, 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.