Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3754C>G (p.Leu1252Val)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(2)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(1)
Uncertain significance(1); Likely benign(1)
2
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.3754C>G (p.Leu1252Val)
Variation ID: 1734589 Accession: VCV001734589.4
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43091777 (GRCh38) [ NCBI UCSC ] 17: 41243794 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Nov 29, 2022 May 1, 2024 Nov 14, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3754C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu1252Val missense NM_001407571.1:c.3541C>G NP_001394500.1:p.Leu1181Val missense NM_001407581.1:c.3754C>G NP_001394510.1:p.Leu1252Val missense NM_001407582.1:c.3754C>G NP_001394511.1:p.Leu1252Val missense NM_001407583.1:c.3754C>G NP_001394512.1:p.Leu1252Val missense NM_001407585.1:c.3754C>G NP_001394514.1:p.Leu1252Val missense NM_001407587.1:c.3751C>G NP_001394516.1:p.Leu1251Val missense NM_001407590.1:c.3751C>G NP_001394519.1:p.Leu1251Val missense NM_001407591.1:c.3751C>G NP_001394520.1:p.Leu1251Val missense NM_001407593.1:c.3754C>G NP_001394522.1:p.Leu1252Val missense NM_001407594.1:c.3754C>G NP_001394523.1:p.Leu1252Val missense NM_001407596.1:c.3754C>G NP_001394525.1:p.Leu1252Val missense NM_001407597.1:c.3754C>G NP_001394526.1:p.Leu1252Val missense NM_001407598.1:c.3754C>G NP_001394527.1:p.Leu1252Val missense NM_001407602.1:c.3754C>G NP_001394531.1:p.Leu1252Val missense NM_001407603.1:c.3754C>G NP_001394532.1:p.Leu1252Val missense NM_001407605.1:c.3754C>G NP_001394534.1:p.Leu1252Val missense NM_001407610.1:c.3751C>G NP_001394539.1:p.Leu1251Val missense NM_001407611.1:c.3751C>G NP_001394540.1:p.Leu1251Val missense NM_001407612.1:c.3751C>G NP_001394541.1:p.Leu1251Val missense NM_001407613.1:c.3751C>G NP_001394542.1:p.Leu1251Val missense NM_001407614.1:c.3751C>G NP_001394543.1:p.Leu1251Val missense NM_001407615.1:c.3751C>G NP_001394544.1:p.Leu1251Val missense NM_001407616.1:c.3754C>G NP_001394545.1:p.Leu1252Val missense NM_001407617.1:c.3754C>G NP_001394546.1:p.Leu1252Val missense NM_001407618.1:c.3754C>G NP_001394547.1:p.Leu1252Val missense NM_001407619.1:c.3754C>G NP_001394548.1:p.Leu1252Val missense NM_001407620.1:c.3754C>G NP_001394549.1:p.Leu1252Val missense NM_001407621.1:c.3754C>G NP_001394550.1:p.Leu1252Val missense NM_001407622.1:c.3754C>G NP_001394551.1:p.Leu1252Val missense NM_001407623.1:c.3754C>G NP_001394552.1:p.Leu1252Val missense NM_001407624.1:c.3754C>G NP_001394553.1:p.Leu1252Val missense NM_001407625.1:c.3754C>G NP_001394554.1:p.Leu1252Val missense NM_001407626.1:c.3754C>G NP_001394555.1:p.Leu1252Val missense NM_001407627.1:c.3751C>G NP_001394556.1:p.Leu1251Val missense NM_001407628.1:c.3751C>G NP_001394557.1:p.Leu1251Val missense NM_001407629.1:c.3751C>G NP_001394558.1:p.Leu1251Val missense NM_001407630.1:c.3751C>G NP_001394559.1:p.Leu1251Val missense NM_001407631.1:c.3751C>G NP_001394560.1:p.Leu1251Val missense NM_001407632.1:c.3751C>G NP_001394561.1:p.Leu1251Val missense NM_001407633.1:c.3751C>G NP_001394562.1:p.Leu1251Val missense NM_001407634.1:c.3751C>G NP_001394563.1:p.Leu1251Val missense NM_001407635.1:c.3751C>G NP_001394564.1:p.Leu1251Val missense NM_001407636.1:c.3751C>G NP_001394565.1:p.Leu1251Val missense NM_001407637.1:c.3751C>G NP_001394566.1:p.Leu1251Val missense NM_001407638.1:c.3751C>G NP_001394567.1:p.Leu1251Val missense NM_001407639.1:c.3754C>G NP_001394568.1:p.Leu1252Val missense NM_001407640.1:c.3754C>G NP_001394569.1:p.Leu1252Val missense NM_001407641.1:c.3754C>G NP_001394570.1:p.Leu1252Val missense NM_001407642.1:c.3754C>G NP_001394571.1:p.Leu1252Val missense NM_001407644.1:c.3751C>G NP_001394573.1:p.Leu1251Val missense NM_001407645.1:c.3751C>G NP_001394574.1:p.Leu1251Val missense NM_001407646.1:c.3745C>G NP_001394575.1:p.Leu1249Val missense NM_001407647.1:c.3745C>G NP_001394576.1:p.Leu1249Val missense NM_001407648.1:c.3631C>G NP_001394577.1:p.Leu1211Val missense NM_001407649.1:c.3628C>G NP_001394578.1:p.Leu1210Val missense NM_001407652.1:c.3754C>G NP_001394581.1:p.Leu1252Val missense NM_001407653.1:c.3676C>G NP_001394582.1:p.Leu1226Val missense NM_001407654.1:c.3676C>G NP_001394583.1:p.Leu1226Val missense NM_001407655.1:c.3676C>G NP_001394584.1:p.Leu1226Val missense NM_001407656.1:c.3676C>G NP_001394585.1:p.Leu1226Val missense NM_001407657.1:c.3676C>G NP_001394586.1:p.Leu1226Val missense NM_001407658.1:c.3676C>G NP_001394587.1:p.Leu1226Val missense NM_001407659.1:c.3673C>G NP_001394588.1:p.Leu1225Val missense NM_001407660.1:c.3673C>G NP_001394589.1:p.Leu1225Val missense NM_001407661.1:c.3673C>G NP_001394590.1:p.Leu1225Val missense NM_001407662.1:c.3673C>G NP_001394591.1:p.Leu1225Val missense NM_001407663.1:c.3676C>G NP_001394592.1:p.Leu1226Val missense NM_001407664.1:c.3631C>G NP_001394593.1:p.Leu1211Val missense NM_001407665.1:c.3631C>G NP_001394594.1:p.Leu1211Val missense NM_001407666.1:c.3631C>G NP_001394595.1:p.Leu1211Val missense NM_001407667.1:c.3631C>G NP_001394596.1:p.Leu1211Val missense NM_001407668.1:c.3631C>G NP_001394597.1:p.Leu1211Val missense NM_001407669.1:c.3631C>G NP_001394598.1:p.Leu1211Val missense NM_001407670.1:c.3628C>G NP_001394599.1:p.Leu1210Val missense NM_001407671.1:c.3628C>G NP_001394600.1:p.Leu1210Val missense NM_001407672.1:c.3628C>G NP_001394601.1:p.Leu1210Val missense NM_001407673.1:c.3628C>G NP_001394602.1:p.Leu1210Val missense NM_001407674.1:c.3631C>G NP_001394603.1:p.Leu1211Val missense NM_001407675.1:c.3631C>G NP_001394604.1:p.Leu1211Val missense NM_001407676.1:c.3631C>G NP_001394605.1:p.Leu1211Val missense NM_001407677.1:c.3631C>G NP_001394606.1:p.Leu1211Val missense NM_001407678.1:c.3631C>G NP_001394607.1:p.Leu1211Val missense NM_001407679.1:c.3631C>G NP_001394608.1:p.Leu1211Val missense NM_001407680.1:c.3631C>G NP_001394609.1:p.Leu1211Val missense NM_001407681.1:c.3631C>G NP_001394610.1:p.Leu1211Val missense NM_001407682.1:c.3631C>G NP_001394611.1:p.Leu1211Val missense NM_001407683.1:c.3631C>G NP_001394612.1:p.Leu1211Val missense NM_001407684.1:c.3754C>G NP_001394613.1:p.Leu1252Val missense NM_001407685.1:c.3628C>G NP_001394614.1:p.Leu1210Val missense NM_001407686.1:c.3628C>G NP_001394615.1:p.Leu1210Val missense NM_001407687.1:c.3628C>G NP_001394616.1:p.Leu1210Val missense NM_001407688.1:c.3628C>G NP_001394617.1:p.Leu1210Val missense NM_001407689.1:c.3628C>G NP_001394618.1:p.Leu1210Val missense NM_001407690.1:c.3628C>G NP_001394619.1:p.Leu1210Val missense NM_001407691.1:c.3628C>G NP_001394620.1:p.Leu1210Val missense NM_001407692.1:c.3613C>G NP_001394621.1:p.Leu1205Val missense NM_001407694.1:c.3613C>G NP_001394623.1:p.Leu1205Val missense NM_001407695.1:c.3613C>G NP_001394624.1:p.Leu1205Val missense NM_001407696.1:c.3613C>G NP_001394625.1:p.Leu1205Val missense NM_001407697.1:c.3613C>G NP_001394626.1:p.Leu1205Val missense NM_001407698.1:c.3613C>G NP_001394627.1:p.Leu1205Val missense NM_001407724.1:c.3613C>G NP_001394653.1:p.Leu1205Val missense NM_001407725.1:c.3613C>G NP_001394654.1:p.Leu1205Val missense NM_001407726.1:c.3613C>G NP_001394655.1:p.Leu1205Val missense NM_001407727.1:c.3613C>G NP_001394656.1:p.Leu1205Val missense NM_001407728.1:c.3613C>G NP_001394657.1:p.Leu1205Val missense NM_001407729.1:c.3613C>G NP_001394658.1:p.Leu1205Val missense NM_001407730.1:c.3613C>G NP_001394659.1:p.Leu1205Val missense NM_001407731.1:c.3613C>G NP_001394660.1:p.Leu1205Val missense NM_001407732.1:c.3613C>G NP_001394661.1:p.Leu1205Val missense NM_001407733.1:c.3613C>G NP_001394662.1:p.Leu1205Val missense NM_001407734.1:c.3613C>G NP_001394663.1:p.Leu1205Val missense NM_001407735.1:c.3613C>G NP_001394664.1:p.Leu1205Val missense NM_001407736.1:c.3613C>G NP_001394665.1:p.Leu1205Val missense NM_001407737.1:c.3613C>G NP_001394666.1:p.Leu1205Val missense NM_001407738.1:c.3613C>G NP_001394667.1:p.Leu1205Val missense NM_001407739.1:c.3613C>G NP_001394668.1:p.Leu1205Val missense NM_001407740.1:c.3610C>G NP_001394669.1:p.Leu1204Val missense NM_001407741.1:c.3610C>G NP_001394670.1:p.Leu1204Val missense NM_001407742.1:c.3610C>G NP_001394671.1:p.Leu1204Val missense NM_001407743.1:c.3610C>G NP_001394672.1:p.Leu1204Val missense NM_001407744.1:c.3610C>G NP_001394673.1:p.Leu1204Val missense NM_001407745.1:c.3610C>G NP_001394674.1:p.Leu1204Val missense NM_001407746.1:c.3610C>G NP_001394675.1:p.Leu1204Val missense NM_001407747.1:c.3610C>G NP_001394676.1:p.Leu1204Val missense NM_001407748.1:c.3610C>G NP_001394677.1:p.Leu1204Val missense NM_001407749.1:c.3610C>G NP_001394678.1:p.Leu1204Val missense NM_001407750.1:c.3613C>G NP_001394679.1:p.Leu1205Val missense NM_001407751.1:c.3613C>G NP_001394680.1:p.Leu1205Val missense NM_001407752.1:c.3613C>G NP_001394681.1:p.Leu1205Val missense NM_001407838.1:c.3610C>G NP_001394767.1:p.Leu1204Val missense NM_001407839.1:c.3610C>G NP_001394768.1:p.Leu1204Val missense NM_001407841.1:c.3610C>G NP_001394770.1:p.Leu1204Val missense NM_001407842.1:c.3610C>G NP_001394771.1:p.Leu1204Val missense NM_001407843.1:c.3610C>G NP_001394772.1:p.Leu1204Val missense NM_001407844.1:c.3610C>G NP_001394773.1:p.Leu1204Val missense NM_001407845.1:c.3610C>G NP_001394774.1:p.Leu1204Val missense NM_001407846.1:c.3610C>G NP_001394775.1:p.Leu1204Val missense NM_001407847.1:c.3610C>G NP_001394776.1:p.Leu1204Val missense NM_001407848.1:c.3610C>G NP_001394777.1:p.Leu1204Val missense NM_001407849.1:c.3610C>G NP_001394778.1:p.Leu1204Val missense NM_001407850.1:c.3613C>G NP_001394779.1:p.Leu1205Val missense NM_001407851.1:c.3613C>G NP_001394780.1:p.Leu1205Val missense NM_001407852.1:c.3613C>G NP_001394781.1:p.Leu1205Val missense NM_001407853.1:c.3541C>G NP_001394782.1:p.Leu1181Val missense NM_001407854.1:c.3754C>G NP_001394783.1:p.Leu1252Val missense NM_001407858.1:c.3754C>G NP_001394787.1:p.Leu1252Val missense NM_001407859.1:c.3754C>G NP_001394788.1:p.Leu1252Val missense NM_001407860.1:c.3751C>G NP_001394789.1:p.Leu1251Val missense NM_001407861.1:c.3751C>G NP_001394790.1:p.Leu1251Val missense NM_001407862.1:c.3553C>G NP_001394791.1:p.Leu1185Val missense NM_001407863.1:c.3631C>G NP_001394792.1:p.Leu1211Val missense NM_001407874.1:c.3550C>G NP_001394803.1:p.Leu1184Val missense NM_001407875.1:c.3550C>G NP_001394804.1:p.Leu1184Val missense NM_001407879.1:c.3544C>G NP_001394808.1:p.Leu1182Val missense NM_001407881.1:c.3544C>G NP_001394810.1:p.Leu1182Val missense NM_001407882.1:c.3544C>G NP_001394811.1:p.Leu1182Val missense NM_001407884.1:c.3544C>G NP_001394813.1:p.Leu1182Val missense NM_001407885.1:c.3544C>G NP_001394814.1:p.Leu1182Val missense NM_001407886.1:c.3544C>G NP_001394815.1:p.Leu1182Val missense NM_001407887.1:c.3544C>G NP_001394816.1:p.Leu1182Val missense NM_001407889.1:c.3544C>G NP_001394818.1:p.Leu1182Val missense NM_001407894.1:c.3541C>G NP_001394823.1:p.Leu1181Val missense NM_001407895.1:c.3541C>G NP_001394824.1:p.Leu1181Val missense NM_001407896.1:c.3541C>G NP_001394825.1:p.Leu1181Val missense NM_001407897.1:c.3541C>G NP_001394826.1:p.Leu1181Val missense NM_001407898.1:c.3541C>G NP_001394827.1:p.Leu1181Val missense NM_001407899.1:c.3541C>G NP_001394828.1:p.Leu1181Val missense NM_001407900.1:c.3544C>G NP_001394829.1:p.Leu1182Val missense NM_001407902.1:c.3544C>G NP_001394831.1:p.Leu1182Val missense NM_001407904.1:c.3544C>G NP_001394833.1:p.Leu1182Val missense NM_001407906.1:c.3544C>G NP_001394835.1:p.Leu1182Val missense NM_001407907.1:c.3544C>G NP_001394836.1:p.Leu1182Val missense NM_001407908.1:c.3544C>G NP_001394837.1:p.Leu1182Val missense NM_001407909.1:c.3544C>G NP_001394838.1:p.Leu1182Val missense NM_001407910.1:c.3544C>G NP_001394839.1:p.Leu1182Val missense NM_001407915.1:c.3541C>G NP_001394844.1:p.Leu1181Val missense NM_001407916.1:c.3541C>G NP_001394845.1:p.Leu1181Val missense NM_001407917.1:c.3541C>G NP_001394846.1:p.Leu1181Val missense NM_001407918.1:c.3541C>G NP_001394847.1:p.Leu1181Val missense NM_001407919.1:c.3631C>G NP_001394848.1:p.Leu1211Val missense NM_001407920.1:c.3490C>G NP_001394849.1:p.Leu1164Val missense NM_001407921.1:c.3490C>G NP_001394850.1:p.Leu1164Val missense NM_001407922.1:c.3490C>G NP_001394851.1:p.Leu1164Val missense NM_001407923.1:c.3490C>G NP_001394852.1:p.Leu1164Val missense NM_001407924.1:c.3490C>G NP_001394853.1:p.Leu1164Val missense NM_001407925.1:c.3490C>G NP_001394854.1:p.Leu1164Val missense NM_001407926.1:c.3490C>G NP_001394855.1:p.Leu1164Val missense NM_001407927.1:c.3490C>G NP_001394856.1:p.Leu1164Val missense NM_001407928.1:c.3490C>G NP_001394857.1:p.Leu1164Val missense NM_001407929.1:c.3490C>G NP_001394858.1:p.Leu1164Val missense NM_001407930.1:c.3487C>G NP_001394859.1:p.Leu1163Val missense NM_001407931.1:c.3487C>G NP_001394860.1:p.Leu1163Val missense NM_001407932.1:c.3487C>G NP_001394861.1:p.Leu1163Val missense NM_001407933.1:c.3490C>G NP_001394862.1:p.Leu1164Val missense NM_001407934.1:c.3487C>G NP_001394863.1:p.Leu1163Val missense NM_001407935.1:c.3490C>G NP_001394864.1:p.Leu1164Val missense NM_001407936.1:c.3487C>G NP_001394865.1:p.Leu1163Val missense NM_001407937.1:c.3631C>G NP_001394866.1:p.Leu1211Val missense NM_001407938.1:c.3631C>G NP_001394867.1:p.Leu1211Val missense NM_001407939.1:c.3631C>G NP_001394868.1:p.Leu1211Val missense NM_001407940.1:c.3628C>G NP_001394869.1:p.Leu1210Val missense NM_001407941.1:c.3628C>G NP_001394870.1:p.Leu1210Val missense NM_001407942.1:c.3613C>G NP_001394871.1:p.Leu1205Val missense NM_001407943.1:c.3610C>G NP_001394872.1:p.Leu1204Val missense NM_001407944.1:c.3613C>G NP_001394873.1:p.Leu1205Val missense NM_001407945.1:c.3613C>G NP_001394874.1:p.Leu1205Val missense NM_001407946.1:c.3421C>G NP_001394875.1:p.Leu1141Val missense NM_001407947.1:c.3421C>G NP_001394876.1:p.Leu1141Val missense NM_001407948.1:c.3421C>G NP_001394877.1:p.Leu1141Val missense NM_001407949.1:c.3421C>G NP_001394878.1:p.Leu1141Val missense NM_001407950.1:c.3421C>G NP_001394879.1:p.Leu1141Val missense NM_001407951.1:c.3421C>G NP_001394880.1:p.Leu1141Val missense NM_001407952.1:c.3421C>G NP_001394881.1:p.Leu1141Val missense NM_001407953.1:c.3421C>G NP_001394882.1:p.Leu1141Val missense NM_001407954.1:c.3418C>G NP_001394883.1:p.Leu1140Val missense NM_001407955.1:c.3418C>G NP_001394884.1:p.Leu1140Val missense NM_001407956.1:c.3418C>G NP_001394885.1:p.Leu1140Val missense NM_001407957.1:c.3421C>G NP_001394886.1:p.Leu1141Val missense NM_001407958.1:c.3418C>G NP_001394887.1:p.Leu1140Val missense NM_001407959.1:c.3373C>G NP_001394888.1:p.Leu1125Val missense NM_001407960.1:c.3373C>G NP_001394889.1:p.Leu1125Val missense NM_001407962.1:c.3370C>G NP_001394891.1:p.Leu1124Val missense NM_001407963.1:c.3373C>G NP_001394892.1:p.Leu1125Val missense NM_001407964.1:c.3610C>G NP_001394893.1:p.Leu1204Val missense NM_001407965.1:c.3250C>G NP_001394894.1:p.Leu1084Val missense NM_001407966.1:c.2866C>G NP_001394895.1:p.Leu956Val missense NM_001407967.1:c.2866C>G NP_001394896.1:p.Leu956Val missense NM_001407968.1:c.1150C>G NP_001394897.1:p.Leu384Val missense NM_001407969.1:c.1150C>G NP_001394898.1:p.Leu384Val missense NM_001407970.1:c.788-745C>G intron variant NM_001407971.1:c.788-745C>G intron variant NM_001407972.1:c.785-745C>G intron variant NM_001407973.1:c.788-745C>G intron variant NM_001407974.1:c.788-745C>G intron variant NM_001407975.1:c.788-745C>G intron variant NM_001407976.1:c.788-745C>G intron variant NM_001407977.1:c.788-745C>G intron variant NM_001407978.1:c.788-745C>G intron variant NM_001407979.1:c.788-745C>G intron variant NM_001407980.1:c.788-745C>G intron variant NM_001407981.1:c.788-745C>G intron variant NM_001407982.1:c.788-745C>G intron variant NM_001407983.1:c.788-745C>G intron variant NM_001407984.1:c.785-745C>G intron variant NM_001407985.1:c.785-745C>G intron variant NM_001407986.1:c.785-745C>G intron variant NM_001407990.1:c.788-745C>G intron variant NM_001407991.1:c.785-745C>G intron variant NM_001407992.1:c.785-745C>G intron variant NM_001407993.1:c.788-745C>G intron variant NM_001408392.1:c.785-745C>G intron variant NM_001408396.1:c.785-745C>G intron variant NM_001408397.1:c.785-745C>G intron variant NM_001408398.1:c.785-745C>G intron variant NM_001408399.1:c.785-745C>G intron variant NM_001408400.1:c.785-745C>G intron variant NM_001408401.1:c.785-745C>G intron variant NM_001408402.1:c.785-745C>G intron variant NM_001408403.1:c.788-745C>G intron variant NM_001408404.1:c.788-745C>G intron variant NM_001408406.1:c.791-754C>G intron variant NM_001408407.1:c.785-745C>G intron variant NM_001408408.1:c.779-745C>G intron variant NM_001408409.1:c.710-745C>G intron variant NM_001408410.1:c.647-745C>G intron variant NM_001408411.1:c.710-745C>G intron variant NM_001408412.1:c.710-745C>G intron variant NM_001408413.1:c.707-745C>G intron variant NM_001408414.1:c.710-745C>G intron variant NM_001408415.1:c.710-745C>G intron variant NM_001408416.1:c.707-745C>G intron variant NM_001408418.1:c.671-745C>G intron variant NM_001408419.1:c.671-745C>G intron variant NM_001408420.1:c.671-745C>G intron variant NM_001408421.1:c.668-745C>G intron variant NM_001408422.1:c.671-745C>G intron variant NM_001408423.1:c.671-745C>G intron variant NM_001408424.1:c.668-745C>G intron variant NM_001408425.1:c.665-745C>G intron variant NM_001408426.1:c.665-745C>G intron variant NM_001408427.1:c.665-745C>G intron variant NM_001408428.1:c.665-745C>G intron variant NM_001408429.1:c.665-745C>G intron variant NM_001408430.1:c.665-745C>G intron variant NM_001408431.1:c.668-745C>G intron variant NM_001408432.1:c.662-745C>G intron variant NM_001408433.1:c.662-745C>G intron variant NM_001408434.1:c.662-745C>G intron variant NM_001408435.1:c.662-745C>G intron variant NM_001408436.1:c.665-745C>G intron variant NM_001408437.1:c.665-745C>G intron variant NM_001408438.1:c.665-745C>G intron variant NM_001408439.1:c.665-745C>G intron variant NM_001408440.1:c.665-745C>G intron variant NM_001408441.1:c.665-745C>G intron variant NM_001408442.1:c.665-745C>G intron variant NM_001408443.1:c.665-745C>G intron variant NM_001408444.1:c.665-745C>G intron variant NM_001408445.1:c.662-745C>G intron variant NM_001408446.1:c.662-745C>G intron variant NM_001408447.1:c.662-745C>G intron variant NM_001408448.1:c.662-745C>G intron variant NM_001408450.1:c.662-745C>G intron variant NM_001408451.1:c.653-745C>G intron variant NM_001408452.1:c.647-745C>G intron variant NM_001408453.1:c.647-745C>G intron variant NM_001408454.1:c.647-745C>G intron variant NM_001408455.1:c.647-745C>G intron variant NM_001408456.1:c.647-745C>G intron variant NM_001408457.1:c.647-745C>G intron variant NM_001408458.1:c.647-745C>G intron variant NM_001408459.1:c.647-745C>G intron variant NM_001408460.1:c.647-745C>G intron variant NM_001408461.1:c.647-745C>G intron variant NM_001408462.1:c.644-745C>G intron variant NM_001408463.1:c.644-745C>G intron variant NM_001408464.1:c.644-745C>G intron variant NM_001408465.1:c.644-745C>G intron variant NM_001408466.1:c.647-745C>G intron variant NM_001408467.1:c.647-745C>G intron variant NM_001408468.1:c.644-745C>G intron variant NM_001408469.1:c.647-745C>G intron variant NM_001408470.1:c.644-745C>G intron variant NM_001408472.1:c.788-745C>G intron variant NM_001408473.1:c.785-745C>G intron variant NM_001408474.1:c.587-745C>G intron variant NM_001408475.1:c.584-745C>G intron variant NM_001408476.1:c.587-745C>G intron variant NM_001408478.1:c.578-745C>G intron variant NM_001408479.1:c.578-745C>G intron variant NM_001408480.1:c.578-745C>G intron variant NM_001408481.1:c.578-745C>G intron variant NM_001408482.1:c.578-745C>G intron variant NM_001408483.1:c.578-745C>G intron variant NM_001408484.1:c.578-745C>G intron variant NM_001408485.1:c.578-745C>G intron variant NM_001408489.1:c.578-745C>G intron variant NM_001408490.1:c.575-745C>G intron variant NM_001408491.1:c.575-745C>G intron variant NM_001408492.1:c.578-745C>G intron variant NM_001408493.1:c.575-745C>G intron variant NM_001408494.1:c.548-745C>G intron variant NM_001408495.1:c.545-745C>G intron variant NM_001408496.1:c.524-745C>G intron variant NM_001408497.1:c.524-745C>G intron variant NM_001408498.1:c.524-745C>G intron variant NM_001408499.1:c.524-745C>G intron variant NM_001408500.1:c.524-745C>G intron variant NM_001408501.1:c.524-745C>G intron variant NM_001408502.1:c.455-745C>G intron variant NM_001408503.1:c.521-745C>G intron variant NM_001408504.1:c.521-745C>G intron variant NM_001408505.1:c.521-745C>G intron variant NM_001408506.1:c.461-745C>G intron variant NM_001408507.1:c.461-745C>G intron variant NM_001408508.1:c.452-745C>G intron variant NM_001408509.1:c.452-745C>G intron variant NM_001408510.1:c.407-745C>G intron variant NM_001408511.1:c.404-745C>G intron variant NM_001408512.1:c.284-745C>G intron variant NM_001408513.1:c.578-745C>G intron variant NM_001408514.1:c.578-745C>G intron variant NM_007297.4:c.3613C>G NP_009228.2:p.Leu1205Val missense NM_007298.4:c.788-745C>G intron variant NM_007299.4:c.788-745C>G intron variant NM_007300.4:c.3754C>G NP_009231.2:p.Leu1252Val missense NR_027676.1:n.3890C>G NC_000017.11:g.43091777G>C NC_000017.10:g.41243794G>C NG_005905.2:g.126207C>G NG_087068.1:g.759G>C LRG_292:g.126207C>G LRG_292t1:c.3754C>G LRG_292p1:p.Leu1252Val - Protein change
- L1163V, L1185V, L1204V, L1210V, L1211V, L1252V, L384V, L1141V, L1205V, L1251V, L1084V, L1125V, L1164V, L1182V, L956V, L1124V, L1140V, L1181V, L1184V, L1225V, L1226V, L1249V
- Other names
- -
- Canonical SPDI
- NC_000017.11:43091776: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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13041 | 14847 | |
| LOC126862571 | - | - | - | GRCh38 | - | 1651 |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Nov 14, 2023 | RCV002363811.6 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003848161.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
|
|
Uncertain significance
(Nov 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002625885.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.L1252V variant (also known as c.3754C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide … (more)
The p.L1252V variant (also known as c.3754C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 3754. The leucine at codon 1252 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, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The p.L1252V variant (also known as c.3754C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 3754. The leucine at codon 1252 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, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
The p.L1252V variant (also known as c.3754C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 3754. The leucine at codon 1252 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, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
Text-mined citations for this variant ...
HelpRecord last updated May 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.