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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 1412 of the BRCA1 protein (p.Ala1412Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4234G>C (p.Ala1412Pro)
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.
(1)
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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4234G>C (p.Ala1412Pro)
Variation ID: 650035 Accession: VCV000650035.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43082527 (GRCh38) [ NCBI UCSC ] 17: 41234544 (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 Aug 14, 2019 Feb 14, 2024 Apr 21, 2021 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4234G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1412Pro missense NM_001407571.1:c.4021G>C NP_001394500.1:p.Ala1341Pro missense NM_001407581.1:c.4234G>C NP_001394510.1:p.Ala1412Pro missense NM_001407582.1:c.4234G>C NP_001394511.1:p.Ala1412Pro missense NM_001407583.1:c.4234G>C NP_001394512.1:p.Ala1412Pro missense NM_001407585.1:c.4234G>C NP_001394514.1:p.Ala1412Pro missense NM_001407587.1:c.4231G>C NP_001394516.1:p.Ala1411Pro missense NM_001407590.1:c.4231G>C NP_001394519.1:p.Ala1411Pro missense NM_001407591.1:c.4231G>C NP_001394520.1:p.Ala1411Pro missense NM_001407593.1:c.4234G>C NP_001394522.1:p.Ala1412Pro missense NM_001407594.1:c.4234G>C NP_001394523.1:p.Ala1412Pro missense NM_001407596.1:c.4234G>C NP_001394525.1:p.Ala1412Pro missense NM_001407597.1:c.4234G>C NP_001394526.1:p.Ala1412Pro missense NM_001407598.1:c.4234G>C NP_001394527.1:p.Ala1412Pro missense NM_001407602.1:c.4234G>C NP_001394531.1:p.Ala1412Pro missense NM_001407603.1:c.4234G>C NP_001394532.1:p.Ala1412Pro missense NM_001407605.1:c.4234G>C NP_001394534.1:p.Ala1412Pro missense NM_001407610.1:c.4231G>C NP_001394539.1:p.Ala1411Pro missense NM_001407611.1:c.4231G>C NP_001394540.1:p.Ala1411Pro missense NM_001407612.1:c.4231G>C NP_001394541.1:p.Ala1411Pro missense NM_001407613.1:c.4231G>C NP_001394542.1:p.Ala1411Pro missense NM_001407614.1:c.4231G>C NP_001394543.1:p.Ala1411Pro missense NM_001407615.1:c.4231G>C NP_001394544.1:p.Ala1411Pro missense NM_001407616.1:c.4234G>C NP_001394545.1:p.Ala1412Pro missense NM_001407617.1:c.4234G>C NP_001394546.1:p.Ala1412Pro missense NM_001407618.1:c.4234G>C NP_001394547.1:p.Ala1412Pro missense NM_001407619.1:c.4234G>C NP_001394548.1:p.Ala1412Pro missense NM_001407620.1:c.4234G>C NP_001394549.1:p.Ala1412Pro missense NM_001407621.1:c.4234G>C NP_001394550.1:p.Ala1412Pro missense NM_001407622.1:c.4234G>C NP_001394551.1:p.Ala1412Pro missense NM_001407623.1:c.4234G>C NP_001394552.1:p.Ala1412Pro missense NM_001407624.1:c.4231G>C NP_001394553.1:p.Ala1411Pro missense NM_001407625.1:c.4231G>C NP_001394554.1:p.Ala1411Pro missense NM_001407626.1:c.4231G>C NP_001394555.1:p.Ala1411Pro missense NM_001407627.1:c.4228G>C NP_001394556.1:p.Ala1410Pro missense NM_001407628.1:c.4228G>C NP_001394557.1:p.Ala1410Pro missense NM_001407629.1:c.4228G>C NP_001394558.1:p.Ala1410Pro missense NM_001407630.1:c.4228G>C NP_001394559.1:p.Ala1410Pro missense NM_001407631.1:c.4228G>C NP_001394560.1:p.Ala1410Pro missense NM_001407632.1:c.4228G>C NP_001394561.1:p.Ala1410Pro missense NM_001407633.1:c.4231G>C NP_001394562.1:p.Ala1411Pro missense NM_001407634.1:c.4231G>C NP_001394563.1:p.Ala1411Pro missense NM_001407635.1:c.4231G>C NP_001394564.1:p.Ala1411Pro missense NM_001407636.1:c.4231G>C NP_001394565.1:p.Ala1411Pro missense NM_001407637.1:c.4231G>C NP_001394566.1:p.Ala1411Pro missense NM_001407638.1:c.4231G>C NP_001394567.1:p.Ala1411Pro missense NM_001407639.1:c.4231G>C NP_001394568.1:p.Ala1411Pro missense NM_001407640.1:c.4231G>C NP_001394569.1:p.Ala1411Pro missense NM_001407641.1:c.4231G>C NP_001394570.1:p.Ala1411Pro missense NM_001407642.1:c.4231G>C NP_001394571.1:p.Ala1411Pro missense NM_001407644.1:c.4228G>C NP_001394573.1:p.Ala1410Pro missense NM_001407645.1:c.4228G>C NP_001394574.1:p.Ala1410Pro missense NM_001407646.1:c.4222G>C NP_001394575.1:p.Ala1408Pro missense NM_001407647.1:c.4222G>C NP_001394576.1:p.Ala1408Pro missense NM_001407648.1:c.4111G>C NP_001394577.1:p.Ala1371Pro missense NM_001407649.1:c.4108G>C NP_001394578.1:p.Ala1370Pro missense NM_001407652.1:c.4234G>C NP_001394581.1:p.Ala1412Pro missense NM_001407653.1:c.4156G>C NP_001394582.1:p.Ala1386Pro missense NM_001407654.1:c.4156G>C NP_001394583.1:p.Ala1386Pro missense NM_001407655.1:c.4156G>C NP_001394584.1:p.Ala1386Pro missense NM_001407656.1:c.4153G>C NP_001394585.1:p.Ala1385Pro missense NM_001407657.1:c.4156G>C NP_001394586.1:p.Ala1386Pro missense NM_001407658.1:c.4156G>C NP_001394587.1:p.Ala1386Pro missense NM_001407659.1:c.4150G>C NP_001394588.1:p.Ala1384Pro missense NM_001407660.1:c.4150G>C NP_001394589.1:p.Ala1384Pro missense NM_001407661.1:c.4153G>C NP_001394590.1:p.Ala1385Pro missense NM_001407662.1:c.4153G>C NP_001394591.1:p.Ala1385Pro missense NM_001407663.1:c.4153G>C NP_001394592.1:p.Ala1385Pro missense NM_001407664.1:c.4111G>C NP_001394593.1:p.Ala1371Pro missense NM_001407665.1:c.4111G>C NP_001394594.1:p.Ala1371Pro missense NM_001407666.1:c.4111G>C NP_001394595.1:p.Ala1371Pro missense NM_001407667.1:c.4111G>C NP_001394596.1:p.Ala1371Pro missense NM_001407668.1:c.4111G>C NP_001394597.1:p.Ala1371Pro missense NM_001407669.1:c.4111G>C NP_001394598.1:p.Ala1371Pro missense NM_001407670.1:c.4108G>C NP_001394599.1:p.Ala1370Pro missense NM_001407671.1:c.4108G>C NP_001394600.1:p.Ala1370Pro missense NM_001407672.1:c.4108G>C NP_001394601.1:p.Ala1370Pro missense NM_001407673.1:c.4108G>C NP_001394602.1:p.Ala1370Pro missense NM_001407674.1:c.4108G>C NP_001394603.1:p.Ala1370Pro missense NM_001407675.1:c.4108G>C NP_001394604.1:p.Ala1370Pro missense NM_001407676.1:c.4108G>C NP_001394605.1:p.Ala1370Pro missense NM_001407677.1:c.4111G>C NP_001394606.1:p.Ala1371Pro missense NM_001407678.1:c.4111G>C NP_001394607.1:p.Ala1371Pro missense NM_001407679.1:c.4111G>C NP_001394608.1:p.Ala1371Pro missense NM_001407680.1:c.4111G>C NP_001394609.1:p.Ala1371Pro missense NM_001407681.1:c.4108G>C NP_001394610.1:p.Ala1370Pro missense NM_001407682.1:c.4108G>C NP_001394611.1:p.Ala1370Pro missense NM_001407683.1:c.4108G>C NP_001394612.1:p.Ala1370Pro missense NM_001407684.1:c.4234G>C NP_001394613.1:p.Ala1412Pro missense NM_001407685.1:c.4105G>C NP_001394614.1:p.Ala1369Pro missense NM_001407686.1:c.4105G>C NP_001394615.1:p.Ala1369Pro missense NM_001407687.1:c.4105G>C NP_001394616.1:p.Ala1369Pro missense NM_001407688.1:c.4108G>C NP_001394617.1:p.Ala1370Pro missense NM_001407689.1:c.4108G>C NP_001394618.1:p.Ala1370Pro missense NM_001407690.1:c.4105G>C NP_001394619.1:p.Ala1369Pro missense NM_001407691.1:c.4105G>C NP_001394620.1:p.Ala1369Pro missense NM_001407692.1:c.4093G>C NP_001394621.1:p.Ala1365Pro missense NM_001407694.1:c.4093G>C NP_001394623.1:p.Ala1365Pro missense NM_001407695.1:c.4093G>C NP_001394624.1:p.Ala1365Pro missense NM_001407696.1:c.4093G>C NP_001394625.1:p.Ala1365Pro missense NM_001407697.1:c.4093G>C NP_001394626.1:p.Ala1365Pro missense NM_001407698.1:c.4093G>C NP_001394627.1:p.Ala1365Pro missense NM_001407724.1:c.4093G>C NP_001394653.1:p.Ala1365Pro missense NM_001407725.1:c.4093G>C NP_001394654.1:p.Ala1365Pro missense NM_001407726.1:c.4093G>C NP_001394655.1:p.Ala1365Pro missense NM_001407727.1:c.4093G>C NP_001394656.1:p.Ala1365Pro missense NM_001407728.1:c.4093G>C NP_001394657.1:p.Ala1365Pro missense NM_001407729.1:c.4093G>C NP_001394658.1:p.Ala1365Pro missense NM_001407730.1:c.4093G>C NP_001394659.1:p.Ala1365Pro missense NM_001407731.1:c.4093G>C NP_001394660.1:p.Ala1365Pro missense NM_001407732.1:c.4093G>C NP_001394661.1:p.Ala1365Pro missense NM_001407733.1:c.4093G>C NP_001394662.1:p.Ala1365Pro missense NM_001407734.1:c.4093G>C NP_001394663.1:p.Ala1365Pro missense NM_001407735.1:c.4093G>C NP_001394664.1:p.Ala1365Pro missense NM_001407736.1:c.4093G>C NP_001394665.1:p.Ala1365Pro missense NM_001407737.1:c.4093G>C NP_001394666.1:p.Ala1365Pro missense NM_001407738.1:c.4093G>C NP_001394667.1:p.Ala1365Pro missense NM_001407739.1:c.4093G>C NP_001394668.1:p.Ala1365Pro missense NM_001407740.1:c.4090G>C NP_001394669.1:p.Ala1364Pro missense NM_001407741.1:c.4090G>C NP_001394670.1:p.Ala1364Pro missense NM_001407742.1:c.4090G>C NP_001394671.1:p.Ala1364Pro missense NM_001407743.1:c.4090G>C NP_001394672.1:p.Ala1364Pro missense NM_001407744.1:c.4090G>C NP_001394673.1:p.Ala1364Pro missense NM_001407745.1:c.4090G>C NP_001394674.1:p.Ala1364Pro missense NM_001407746.1:c.4090G>C NP_001394675.1:p.Ala1364Pro missense NM_001407747.1:c.4090G>C NP_001394676.1:p.Ala1364Pro missense NM_001407748.1:c.4090G>C NP_001394677.1:p.Ala1364Pro missense NM_001407749.1:c.4090G>C NP_001394678.1:p.Ala1364Pro missense NM_001407750.1:c.4090G>C NP_001394679.1:p.Ala1364Pro missense NM_001407751.1:c.4090G>C NP_001394680.1:p.Ala1364Pro missense NM_001407752.1:c.4090G>C NP_001394681.1:p.Ala1364Pro missense NM_001407838.1:c.4090G>C NP_001394767.1:p.Ala1364Pro missense NM_001407839.1:c.4090G>C NP_001394768.1:p.Ala1364Pro missense NM_001407841.1:c.4090G>C NP_001394770.1:p.Ala1364Pro missense NM_001407842.1:c.4090G>C NP_001394771.1:p.Ala1364Pro missense NM_001407843.1:c.4090G>C NP_001394772.1:p.Ala1364Pro missense NM_001407844.1:c.4090G>C NP_001394773.1:p.Ala1364Pro missense NM_001407845.1:c.4090G>C NP_001394774.1:p.Ala1364Pro missense NM_001407846.1:c.4090G>C NP_001394775.1:p.Ala1364Pro missense NM_001407847.1:c.4087G>C NP_001394776.1:p.Ala1363Pro missense NM_001407848.1:c.4087G>C NP_001394777.1:p.Ala1363Pro missense NM_001407849.1:c.4087G>C NP_001394778.1:p.Ala1363Pro missense NM_001407850.1:c.4090G>C NP_001394779.1:p.Ala1364Pro missense NM_001407851.1:c.4090G>C NP_001394780.1:p.Ala1364Pro missense NM_001407852.1:c.4090G>C NP_001394781.1:p.Ala1364Pro missense NM_001407853.1:c.4021G>C NP_001394782.1:p.Ala1341Pro missense NM_001407854.1:c.4234G>C NP_001394783.1:p.Ala1412Pro missense NM_001407858.1:c.4234G>C NP_001394787.1:p.Ala1412Pro missense NM_001407859.1:c.4234G>C NP_001394788.1:p.Ala1412Pro missense NM_001407860.1:c.4231G>C NP_001394789.1:p.Ala1411Pro missense NM_001407861.1:c.4231G>C NP_001394790.1:p.Ala1411Pro missense NM_001407862.1:c.4033G>C NP_001394791.1:p.Ala1345Pro missense NM_001407863.1:c.4111G>C NP_001394792.1:p.Ala1371Pro missense NM_001407874.1:c.4030G>C NP_001394803.1:p.Ala1344Pro missense NM_001407875.1:c.4030G>C NP_001394804.1:p.Ala1344Pro missense NM_001407879.1:c.4024G>C NP_001394808.1:p.Ala1342Pro missense NM_001407881.1:c.4024G>C NP_001394810.1:p.Ala1342Pro missense NM_001407882.1:c.4024G>C NP_001394811.1:p.Ala1342Pro missense NM_001407884.1:c.4024G>C NP_001394813.1:p.Ala1342Pro missense NM_001407885.1:c.4024G>C NP_001394814.1:p.Ala1342Pro missense NM_001407886.1:c.4024G>C NP_001394815.1:p.Ala1342Pro missense NM_001407887.1:c.4024G>C NP_001394816.1:p.Ala1342Pro missense NM_001407889.1:c.4024G>C NP_001394818.1:p.Ala1342Pro missense NM_001407894.1:c.4021G>C NP_001394823.1:p.Ala1341Pro missense NM_001407895.1:c.4021G>C NP_001394824.1:p.Ala1341Pro missense NM_001407896.1:c.4021G>C NP_001394825.1:p.Ala1341Pro missense NM_001407897.1:c.4021G>C NP_001394826.1:p.Ala1341Pro missense NM_001407898.1:c.4021G>C NP_001394827.1:p.Ala1341Pro missense NM_001407899.1:c.4021G>C NP_001394828.1:p.Ala1341Pro missense NM_001407900.1:c.4024G>C NP_001394829.1:p.Ala1342Pro missense NM_001407902.1:c.4024G>C NP_001394831.1:p.Ala1342Pro missense NM_001407904.1:c.4024G>C NP_001394833.1:p.Ala1342Pro missense NM_001407906.1:c.4024G>C NP_001394835.1:p.Ala1342Pro missense NM_001407907.1:c.4021G>C NP_001394836.1:p.Ala1341Pro missense NM_001407908.1:c.4021G>C NP_001394837.1:p.Ala1341Pro missense NM_001407909.1:c.4021G>C NP_001394838.1:p.Ala1341Pro missense NM_001407910.1:c.4021G>C NP_001394839.1:p.Ala1341Pro missense NM_001407915.1:c.4018G>C NP_001394844.1:p.Ala1340Pro missense NM_001407916.1:c.4021G>C NP_001394845.1:p.Ala1341Pro missense NM_001407917.1:c.4021G>C NP_001394846.1:p.Ala1341Pro missense NM_001407918.1:c.4021G>C NP_001394847.1:p.Ala1341Pro missense NM_001407919.1:c.4111G>C NP_001394848.1:p.Ala1371Pro missense NM_001407920.1:c.3970G>C NP_001394849.1:p.Ala1324Pro missense NM_001407921.1:c.3970G>C NP_001394850.1:p.Ala1324Pro missense NM_001407922.1:c.3970G>C NP_001394851.1:p.Ala1324Pro missense NM_001407923.1:c.3970G>C NP_001394852.1:p.Ala1324Pro missense NM_001407924.1:c.3970G>C NP_001394853.1:p.Ala1324Pro missense NM_001407925.1:c.3970G>C NP_001394854.1:p.Ala1324Pro missense NM_001407926.1:c.3970G>C NP_001394855.1:p.Ala1324Pro missense NM_001407927.1:c.3970G>C NP_001394856.1:p.Ala1324Pro missense NM_001407928.1:c.3970G>C NP_001394857.1:p.Ala1324Pro missense NM_001407929.1:c.3970G>C NP_001394858.1:p.Ala1324Pro missense NM_001407930.1:c.3967G>C NP_001394859.1:p.Ala1323Pro missense NM_001407931.1:c.3967G>C NP_001394860.1:p.Ala1323Pro missense NM_001407932.1:c.3967G>C NP_001394861.1:p.Ala1323Pro missense NM_001407933.1:c.3967G>C NP_001394862.1:p.Ala1323Pro missense NM_001407934.1:c.3964G>C NP_001394863.1:p.Ala1322Pro missense NM_001407935.1:c.3967G>C NP_001394864.1:p.Ala1323Pro missense NM_001407936.1:c.3967G>C NP_001394865.1:p.Ala1323Pro missense NM_001407937.1:c.4111G>C NP_001394866.1:p.Ala1371Pro missense NM_001407938.1:c.4111G>C NP_001394867.1:p.Ala1371Pro missense NM_001407939.1:c.4111G>C NP_001394868.1:p.Ala1371Pro missense NM_001407940.1:c.4108G>C NP_001394869.1:p.Ala1370Pro missense NM_001407941.1:c.4108G>C NP_001394870.1:p.Ala1370Pro missense NM_001407942.1:c.4093G>C NP_001394871.1:p.Ala1365Pro missense NM_001407943.1:c.4090G>C NP_001394872.1:p.Ala1364Pro missense NM_001407944.1:c.4093G>C NP_001394873.1:p.Ala1365Pro missense NM_001407945.1:c.4093G>C NP_001394874.1:p.Ala1365Pro missense NM_001407946.1:c.3901G>C NP_001394875.1:p.Ala1301Pro missense NM_001407947.1:c.3901G>C NP_001394876.1:p.Ala1301Pro missense NM_001407948.1:c.3901G>C NP_001394877.1:p.Ala1301Pro missense NM_001407949.1:c.3901G>C NP_001394878.1:p.Ala1301Pro missense NM_001407950.1:c.3901G>C NP_001394879.1:p.Ala1301Pro missense NM_001407951.1:c.3901G>C NP_001394880.1:p.Ala1301Pro missense NM_001407952.1:c.3898G>C NP_001394881.1:p.Ala1300Pro missense NM_001407953.1:c.3898G>C NP_001394882.1:p.Ala1300Pro missense NM_001407954.1:c.3898G>C NP_001394883.1:p.Ala1300Pro missense NM_001407955.1:c.3898G>C NP_001394884.1:p.Ala1300Pro missense NM_001407956.1:c.3895G>C NP_001394885.1:p.Ala1299Pro missense NM_001407957.1:c.3898G>C NP_001394886.1:p.Ala1300Pro missense NM_001407958.1:c.3898G>C NP_001394887.1:p.Ala1300Pro missense NM_001407959.1:c.3853G>C NP_001394888.1:p.Ala1285Pro missense NM_001407960.1:c.3853G>C NP_001394889.1:p.Ala1285Pro missense NM_001407962.1:c.3850G>C NP_001394891.1:p.Ala1284Pro missense NM_001407963.1:c.3850G>C NP_001394892.1:p.Ala1284Pro missense NM_001407964.1:c.4090G>C NP_001394893.1:p.Ala1364Pro missense NM_001407965.1:c.3727G>C NP_001394894.1:p.Ala1243Pro missense NM_001407966.1:c.3346G>C NP_001394895.1:p.Ala1116Pro missense NM_001407967.1:c.3346G>C NP_001394896.1:p.Ala1116Pro missense NM_001407968.1:c.1630G>C NP_001394897.1:p.Ala544Pro missense NM_001407969.1:c.1627G>C NP_001394898.1:p.Ala543Pro missense NM_001407970.1:c.925G>C NP_001394899.1:p.Ala309Pro missense NM_001407971.1:c.925G>C NP_001394900.1:p.Ala309Pro missense NM_001407972.1:c.922G>C NP_001394901.1:p.Ala308Pro missense NM_001407973.1:c.925G>C NP_001394902.1:p.Ala309Pro missense NM_001407974.1:c.925G>C NP_001394903.1:p.Ala309Pro missense NM_001407975.1:c.925G>C NP_001394904.1:p.Ala309Pro missense NM_001407976.1:c.925G>C NP_001394905.1:p.Ala309Pro missense NM_001407977.1:c.925G>C NP_001394906.1:p.Ala309Pro missense NM_001407978.1:c.925G>C NP_001394907.1:p.Ala309Pro missense NM_001407979.1:c.922G>C NP_001394908.1:p.Ala308Pro missense NM_001407980.1:c.922G>C NP_001394909.1:p.Ala308Pro missense NM_001407981.1:c.922G>C NP_001394910.1:p.Ala308Pro missense NM_001407982.1:c.922G>C NP_001394911.1:p.Ala308Pro missense NM_001407983.1:c.922G>C NP_001394912.1:p.Ala308Pro missense NM_001407984.1:c.922G>C NP_001394913.1:p.Ala308Pro missense NM_001407985.1:c.922G>C NP_001394914.1:p.Ala308Pro missense NM_001407986.1:c.922G>C NP_001394915.1:p.Ala308Pro missense NM_001407990.1:c.922G>C NP_001394919.1:p.Ala308Pro missense NM_001407991.1:c.922G>C NP_001394920.1:p.Ala308Pro missense NM_001407992.1:c.922G>C NP_001394921.1:p.Ala308Pro missense NM_001407993.1:c.925G>C NP_001394922.1:p.Ala309Pro missense NM_001408392.1:c.922G>C NP_001395321.1:p.Ala308Pro missense NM_001408396.1:c.922G>C NP_001395325.1:p.Ala308Pro missense NM_001408397.1:c.922G>C NP_001395326.1:p.Ala308Pro missense NM_001408398.1:c.922G>C NP_001395327.1:p.Ala308Pro missense NM_001408399.1:c.922G>C NP_001395328.1:p.Ala308Pro missense NM_001408400.1:c.919G>C NP_001395329.1:p.Ala307Pro missense NM_001408401.1:c.919G>C NP_001395330.1:p.Ala307Pro missense NM_001408402.1:c.919G>C NP_001395331.1:p.Ala307Pro missense NM_001408403.1:c.922G>C NP_001395332.1:p.Ala308Pro missense NM_001408404.1:c.922G>C NP_001395333.1:p.Ala308Pro missense NM_001408406.1:c.916G>C NP_001395335.1:p.Ala306Pro missense NM_001408407.1:c.919G>C NP_001395336.1:p.Ala307Pro missense NM_001408408.1:c.916G>C NP_001395337.1:p.Ala306Pro missense NM_001408409.1:c.847G>C NP_001395338.1:p.Ala283Pro missense NM_001408410.1:c.784G>C NP_001395339.1:p.Ala262Pro missense NM_001408411.1:c.847G>C NP_001395340.1:p.Ala283Pro missense NM_001408412.1:c.847G>C NP_001395341.1:p.Ala283Pro missense NM_001408413.1:c.844G>C NP_001395342.1:p.Ala282Pro missense NM_001408414.1:c.847G>C NP_001395343.1:p.Ala283Pro missense NM_001408415.1:c.847G>C NP_001395344.1:p.Ala283Pro missense NM_001408416.1:c.844G>C NP_001395345.1:p.Ala282Pro missense NM_001408418.1:c.808G>C NP_001395347.1:p.Ala270Pro missense NM_001408419.1:c.808G>C NP_001395348.1:p.Ala270Pro missense NM_001408420.1:c.808G>C NP_001395349.1:p.Ala270Pro missense NM_001408421.1:c.805G>C NP_001395350.1:p.Ala269Pro missense NM_001408422.1:c.808G>C NP_001395351.1:p.Ala270Pro missense NM_001408423.1:c.808G>C NP_001395352.1:p.Ala270Pro missense NM_001408424.1:c.805G>C NP_001395353.1:p.Ala269Pro missense NM_001408425.1:c.802G>C NP_001395354.1:p.Ala268Pro missense NM_001408426.1:c.802G>C NP_001395355.1:p.Ala268Pro missense NM_001408427.1:c.802G>C NP_001395356.1:p.Ala268Pro missense NM_001408428.1:c.802G>C NP_001395357.1:p.Ala268Pro missense NM_001408429.1:c.802G>C NP_001395358.1:p.Ala268Pro missense NM_001408430.1:c.802G>C NP_001395359.1:p.Ala268Pro missense NM_001408431.1:c.805G>C NP_001395360.1:p.Ala269Pro missense NM_001408432.1:c.799G>C NP_001395361.1:p.Ala267Pro missense NM_001408433.1:c.799G>C NP_001395362.1:p.Ala267Pro missense NM_001408434.1:c.799G>C NP_001395363.1:p.Ala267Pro missense NM_001408435.1:c.799G>C NP_001395364.1:p.Ala267Pro missense NM_001408436.1:c.802G>C NP_001395365.1:p.Ala268Pro missense NM_001408437.1:c.802G>C NP_001395366.1:p.Ala268Pro missense NM_001408438.1:c.802G>C NP_001395367.1:p.Ala268Pro missense NM_001408439.1:c.802G>C NP_001395368.1:p.Ala268Pro missense NM_001408440.1:c.802G>C NP_001395369.1:p.Ala268Pro missense NM_001408441.1:c.799G>C NP_001395370.1:p.Ala267Pro missense NM_001408442.1:c.799G>C NP_001395371.1:p.Ala267Pro missense NM_001408443.1:c.799G>C NP_001395372.1:p.Ala267Pro missense NM_001408444.1:c.799G>C NP_001395373.1:p.Ala267Pro missense NM_001408445.1:c.799G>C NP_001395374.1:p.Ala267Pro missense NM_001408446.1:c.799G>C NP_001395375.1:p.Ala267Pro missense NM_001408447.1:c.799G>C NP_001395376.1:p.Ala267Pro missense NM_001408448.1:c.799G>C NP_001395377.1:p.Ala267Pro missense NM_001408450.1:c.799G>C NP_001395379.1:p.Ala267Pro missense NM_001408451.1:c.790G>C NP_001395380.1:p.Ala264Pro missense NM_001408452.1:c.784G>C NP_001395381.1:p.Ala262Pro missense NM_001408453.1:c.784G>C NP_001395382.1:p.Ala262Pro missense NM_001408454.1:c.784G>C NP_001395383.1:p.Ala262Pro missense NM_001408455.1:c.784G>C NP_001395384.1:p.Ala262Pro missense NM_001408456.1:c.784G>C NP_001395385.1:p.Ala262Pro missense NM_001408457.1:c.784G>C NP_001395386.1:p.Ala262Pro missense NM_001408458.1:c.784G>C NP_001395387.1:p.Ala262Pro missense NM_001408459.1:c.784G>C NP_001395388.1:p.Ala262Pro missense NM_001408460.1:c.784G>C NP_001395389.1:p.Ala262Pro missense NM_001408461.1:c.784G>C NP_001395390.1:p.Ala262Pro missense NM_001408462.1:c.781G>C NP_001395391.1:p.Ala261Pro missense NM_001408463.1:c.781G>C NP_001395392.1:p.Ala261Pro missense NM_001408464.1:c.781G>C NP_001395393.1:p.Ala261Pro missense NM_001408465.1:c.781G>C NP_001395394.1:p.Ala261Pro missense NM_001408466.1:c.781G>C NP_001395395.1:p.Ala261Pro missense NM_001408467.1:c.781G>C NP_001395396.1:p.Ala261Pro missense NM_001408468.1:c.781G>C NP_001395397.1:p.Ala261Pro missense NM_001408469.1:c.781G>C NP_001395398.1:p.Ala261Pro missense NM_001408470.1:c.778G>C NP_001395399.1:p.Ala260Pro missense NM_001408472.1:c.922G>C NP_001395401.1:p.Ala308Pro missense NM_001408473.1:c.922G>C NP_001395402.1:p.Ala308Pro missense NM_001408474.1:c.724G>C NP_001395403.1:p.Ala242Pro missense NM_001408475.1:c.721G>C NP_001395404.1:p.Ala241Pro missense NM_001408476.1:c.724G>C NP_001395405.1:p.Ala242Pro missense NM_001408478.1:c.715G>C NP_001395407.1:p.Ala239Pro missense NM_001408479.1:c.715G>C NP_001395408.1:p.Ala239Pro missense NM_001408480.1:c.715G>C NP_001395409.1:p.Ala239Pro missense NM_001408481.1:c.715G>C NP_001395410.1:p.Ala239Pro missense NM_001408482.1:c.715G>C NP_001395411.1:p.Ala239Pro missense NM_001408483.1:c.715G>C NP_001395412.1:p.Ala239Pro missense NM_001408484.1:c.715G>C NP_001395413.1:p.Ala239Pro missense NM_001408485.1:c.715G>C NP_001395414.1:p.Ala239Pro missense NM_001408489.1:c.712G>C NP_001395418.1:p.Ala238Pro missense NM_001408490.1:c.712G>C NP_001395419.1:p.Ala238Pro missense NM_001408491.1:c.712G>C NP_001395420.1:p.Ala238Pro missense NM_001408492.1:c.712G>C NP_001395421.1:p.Ala238Pro missense NM_001408493.1:c.712G>C NP_001395422.1:p.Ala238Pro missense NM_001408494.1:c.685G>C NP_001395423.1:p.Ala229Pro missense NM_001408495.1:c.682G>C NP_001395424.1:p.Ala228Pro missense NM_001408496.1:c.661G>C NP_001395425.1:p.Ala221Pro missense NM_001408497.1:c.661G>C NP_001395426.1:p.Ala221Pro missense NM_001408498.1:c.661G>C NP_001395427.1:p.Ala221Pro missense NM_001408499.1:c.661G>C NP_001395428.1:p.Ala221Pro missense NM_001408500.1:c.661G>C NP_001395429.1:p.Ala221Pro missense NM_001408501.1:c.661G>C NP_001395430.1:p.Ala221Pro missense NM_001408502.1:c.592G>C NP_001395431.1:p.Ala198Pro missense NM_001408503.1:c.658G>C NP_001395432.1:p.Ala220Pro missense NM_001408504.1:c.658G>C NP_001395433.1:p.Ala220Pro missense NM_001408505.1:c.658G>C NP_001395434.1:p.Ala220Pro missense NM_001408506.1:c.598G>C NP_001395435.1:p.Ala200Pro missense NM_001408507.1:c.595G>C NP_001395436.1:p.Ala199Pro missense NM_001408508.1:c.586G>C NP_001395437.1:p.Ala196Pro missense NM_001408509.1:c.586G>C NP_001395438.1:p.Ala196Pro missense NM_001408510.1:c.544G>C NP_001395439.1:p.Ala182Pro missense NM_001408511.1:c.541G>C NP_001395440.1:p.Ala181Pro missense NM_001408512.1:c.421G>C NP_001395441.1:p.Ala141Pro missense NM_001408513.1:c.712G>C NP_001395442.1:p.Ala238Pro missense NM_001408514.1:c.715G>C NP_001395443.1:p.Ala239Pro missense NM_007297.4:c.4093G>C NP_009228.2:p.Ala1365Pro missense NM_007298.4:c.925G>C NP_009229.2:p.Ala309Pro missense NM_007299.4:c.925G>C NP_009230.2:p.Ala309Pro missense NM_007300.4:c.4234G>C NP_009231.2:p.Ala1412Pro missense NM_007304.2:c.925G>C NP_009235.2:p.Ala309Pro missense NR_027676.2:n.4411G>C non-coding transcript variant NC_000017.11:g.43082527C>G NC_000017.10:g.41234544C>G NG_005905.2:g.135457G>C LRG_292:g.135457G>C LRG_292t1:c.4234G>C LRG_292p1:p.Ala1412Pro - Protein change
- A1365P, A309P, A1412P, A1300P, A1323P, A1324P, A1363P, A1364P, A1370P, A1386P, A1410P, A182P, A220P, A241P, A242P, A282P, A283P, A1284P, A1285P, A1299P, A1340P, A1345P, A1371P, A1384P, A200P, A228P, A260P, A264P, A269P, A306P, A543P, A544P, A1116P, A1243P, A1301P, A1385P, A141P, A196P, A229P, A238P, A262P, A267P, A270P, A308P, A1322P, A1341P, A1342P, A1344P, A1369P, A1408P, A1411P, A181P, A198P, A199P, A221P, A239P, A261P, A268P, A307P
- Other names
- -
- Canonical SPDI
- NC_000017.11:43082526:C:G
-
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.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
- 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 |
13044 | 14850 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 21, 2021 | RCV000805111.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Apr 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000945055.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 1412 of the BRCA1 protein (p.Ala1412Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. (less)
|
Comment:
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:
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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 1412 of the BRCA1 protein (p.Ala1412Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs765183110 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.