In summary, this variant is a rare missense change that is not expected to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not affect BRCA1 protein function. In BRCA1-null embryonic stem cells, this missense variant was able to restore the proliferation defect of these cells, similar to the wild-type BRCA1 protein (PMID: 23867111). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 55044). This sequence change replaces serine with arginine at codon 1301 of the BRCA1 protein (p.Ser1301Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3903T>A (p.Ser1301Arg)
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.
(6)
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(3); Likely benign(1)
Uncertain significance(3); Likely benign(1)
6
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.3903T>A (p.Ser1301Arg)
Variation ID: 55044 Accession: VCV000055044.14
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091628 (GRCh38) [ NCBI UCSC ] 17: 41243645 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 May 1, 2024 Feb 26, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3903T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ser1301Arg missense NM_001407571.1:c.3690T>A NP_001394500.1:p.Ser1230Arg missense NM_001407581.1:c.3903T>A NP_001394510.1:p.Ser1301Arg missense NM_001407582.1:c.3903T>A NP_001394511.1:p.Ser1301Arg missense NM_001407583.1:c.3903T>A NP_001394512.1:p.Ser1301Arg missense NM_001407585.1:c.3903T>A NP_001394514.1:p.Ser1301Arg missense NM_001407587.1:c.3900T>A NP_001394516.1:p.Ser1300Arg missense NM_001407590.1:c.3900T>A NP_001394519.1:p.Ser1300Arg missense NM_001407591.1:c.3900T>A NP_001394520.1:p.Ser1300Arg missense NM_001407593.1:c.3903T>A NP_001394522.1:p.Ser1301Arg missense NM_001407594.1:c.3903T>A NP_001394523.1:p.Ser1301Arg missense NM_001407596.1:c.3903T>A NP_001394525.1:p.Ser1301Arg missense NM_001407597.1:c.3903T>A NP_001394526.1:p.Ser1301Arg missense NM_001407598.1:c.3903T>A NP_001394527.1:p.Ser1301Arg missense NM_001407602.1:c.3903T>A NP_001394531.1:p.Ser1301Arg missense NM_001407603.1:c.3903T>A NP_001394532.1:p.Ser1301Arg missense NM_001407605.1:c.3903T>A NP_001394534.1:p.Ser1301Arg missense NM_001407610.1:c.3900T>A NP_001394539.1:p.Ser1300Arg missense NM_001407611.1:c.3900T>A NP_001394540.1:p.Ser1300Arg missense NM_001407612.1:c.3900T>A NP_001394541.1:p.Ser1300Arg missense NM_001407613.1:c.3900T>A NP_001394542.1:p.Ser1300Arg missense NM_001407614.1:c.3900T>A NP_001394543.1:p.Ser1300Arg missense NM_001407615.1:c.3900T>A NP_001394544.1:p.Ser1300Arg missense NM_001407616.1:c.3903T>A NP_001394545.1:p.Ser1301Arg missense NM_001407617.1:c.3903T>A NP_001394546.1:p.Ser1301Arg missense NM_001407618.1:c.3903T>A NP_001394547.1:p.Ser1301Arg missense NM_001407619.1:c.3903T>A NP_001394548.1:p.Ser1301Arg missense NM_001407620.1:c.3903T>A NP_001394549.1:p.Ser1301Arg missense NM_001407621.1:c.3903T>A NP_001394550.1:p.Ser1301Arg missense NM_001407622.1:c.3903T>A NP_001394551.1:p.Ser1301Arg missense NM_001407623.1:c.3903T>A NP_001394552.1:p.Ser1301Arg missense NM_001407624.1:c.3903T>A NP_001394553.1:p.Ser1301Arg missense NM_001407625.1:c.3903T>A NP_001394554.1:p.Ser1301Arg missense NM_001407626.1:c.3903T>A NP_001394555.1:p.Ser1301Arg missense NM_001407627.1:c.3900T>A NP_001394556.1:p.Ser1300Arg missense NM_001407628.1:c.3900T>A NP_001394557.1:p.Ser1300Arg missense NM_001407629.1:c.3900T>A NP_001394558.1:p.Ser1300Arg missense NM_001407630.1:c.3900T>A NP_001394559.1:p.Ser1300Arg missense NM_001407631.1:c.3900T>A NP_001394560.1:p.Ser1300Arg missense NM_001407632.1:c.3900T>A NP_001394561.1:p.Ser1300Arg missense NM_001407633.1:c.3900T>A NP_001394562.1:p.Ser1300Arg missense NM_001407634.1:c.3900T>A NP_001394563.1:p.Ser1300Arg missense NM_001407635.1:c.3900T>A NP_001394564.1:p.Ser1300Arg missense NM_001407636.1:c.3900T>A NP_001394565.1:p.Ser1300Arg missense NM_001407637.1:c.3900T>A NP_001394566.1:p.Ser1300Arg missense NM_001407638.1:c.3900T>A NP_001394567.1:p.Ser1300Arg missense NM_001407639.1:c.3903T>A NP_001394568.1:p.Ser1301Arg missense NM_001407640.1:c.3903T>A NP_001394569.1:p.Ser1301Arg missense NM_001407641.1:c.3903T>A NP_001394570.1:p.Ser1301Arg missense NM_001407642.1:c.3903T>A NP_001394571.1:p.Ser1301Arg missense NM_001407644.1:c.3900T>A NP_001394573.1:p.Ser1300Arg missense NM_001407645.1:c.3900T>A NP_001394574.1:p.Ser1300Arg missense NM_001407646.1:c.3894T>A NP_001394575.1:p.Ser1298Arg missense NM_001407647.1:c.3894T>A NP_001394576.1:p.Ser1298Arg missense NM_001407648.1:c.3780T>A NP_001394577.1:p.Ser1260Arg missense NM_001407649.1:c.3777T>A NP_001394578.1:p.Ser1259Arg missense NM_001407652.1:c.3903T>A NP_001394581.1:p.Ser1301Arg missense NM_001407653.1:c.3825T>A NP_001394582.1:p.Ser1275Arg missense NM_001407654.1:c.3825T>A NP_001394583.1:p.Ser1275Arg missense NM_001407655.1:c.3825T>A NP_001394584.1:p.Ser1275Arg missense NM_001407656.1:c.3825T>A NP_001394585.1:p.Ser1275Arg missense NM_001407657.1:c.3825T>A NP_001394586.1:p.Ser1275Arg missense NM_001407658.1:c.3825T>A NP_001394587.1:p.Ser1275Arg missense NM_001407659.1:c.3822T>A NP_001394588.1:p.Ser1274Arg missense NM_001407660.1:c.3822T>A NP_001394589.1:p.Ser1274Arg missense NM_001407661.1:c.3822T>A NP_001394590.1:p.Ser1274Arg missense NM_001407662.1:c.3822T>A NP_001394591.1:p.Ser1274Arg missense NM_001407663.1:c.3825T>A NP_001394592.1:p.Ser1275Arg missense NM_001407664.1:c.3780T>A NP_001394593.1:p.Ser1260Arg missense NM_001407665.1:c.3780T>A NP_001394594.1:p.Ser1260Arg missense NM_001407666.1:c.3780T>A NP_001394595.1:p.Ser1260Arg missense NM_001407667.1:c.3780T>A NP_001394596.1:p.Ser1260Arg missense NM_001407668.1:c.3780T>A NP_001394597.1:p.Ser1260Arg missense NM_001407669.1:c.3780T>A NP_001394598.1:p.Ser1260Arg missense NM_001407670.1:c.3777T>A NP_001394599.1:p.Ser1259Arg missense NM_001407671.1:c.3777T>A NP_001394600.1:p.Ser1259Arg missense NM_001407672.1:c.3777T>A NP_001394601.1:p.Ser1259Arg missense NM_001407673.1:c.3777T>A NP_001394602.1:p.Ser1259Arg missense NM_001407674.1:c.3780T>A NP_001394603.1:p.Ser1260Arg missense NM_001407675.1:c.3780T>A NP_001394604.1:p.Ser1260Arg missense NM_001407676.1:c.3780T>A NP_001394605.1:p.Ser1260Arg missense NM_001407677.1:c.3780T>A NP_001394606.1:p.Ser1260Arg missense NM_001407678.1:c.3780T>A NP_001394607.1:p.Ser1260Arg missense NM_001407679.1:c.3780T>A NP_001394608.1:p.Ser1260Arg missense NM_001407680.1:c.3780T>A NP_001394609.1:p.Ser1260Arg missense NM_001407681.1:c.3780T>A NP_001394610.1:p.Ser1260Arg missense NM_001407682.1:c.3780T>A NP_001394611.1:p.Ser1260Arg missense NM_001407683.1:c.3780T>A NP_001394612.1:p.Ser1260Arg missense NM_001407684.1:c.3903T>A NP_001394613.1:p.Ser1301Arg missense NM_001407685.1:c.3777T>A NP_001394614.1:p.Ser1259Arg missense NM_001407686.1:c.3777T>A NP_001394615.1:p.Ser1259Arg missense NM_001407687.1:c.3777T>A NP_001394616.1:p.Ser1259Arg missense NM_001407688.1:c.3777T>A NP_001394617.1:p.Ser1259Arg missense NM_001407689.1:c.3777T>A NP_001394618.1:p.Ser1259Arg missense NM_001407690.1:c.3777T>A NP_001394619.1:p.Ser1259Arg missense NM_001407691.1:c.3777T>A NP_001394620.1:p.Ser1259Arg missense NM_001407692.1:c.3762T>A NP_001394621.1:p.Ser1254Arg missense NM_001407694.1:c.3762T>A NP_001394623.1:p.Ser1254Arg missense NM_001407695.1:c.3762T>A NP_001394624.1:p.Ser1254Arg missense NM_001407696.1:c.3762T>A NP_001394625.1:p.Ser1254Arg missense NM_001407697.1:c.3762T>A NP_001394626.1:p.Ser1254Arg missense NM_001407698.1:c.3762T>A NP_001394627.1:p.Ser1254Arg missense NM_001407724.1:c.3762T>A NP_001394653.1:p.Ser1254Arg missense NM_001407725.1:c.3762T>A NP_001394654.1:p.Ser1254Arg missense NM_001407726.1:c.3762T>A NP_001394655.1:p.Ser1254Arg missense NM_001407727.1:c.3762T>A NP_001394656.1:p.Ser1254Arg missense NM_001407728.1:c.3762T>A NP_001394657.1:p.Ser1254Arg missense NM_001407729.1:c.3762T>A NP_001394658.1:p.Ser1254Arg missense NM_001407730.1:c.3762T>A NP_001394659.1:p.Ser1254Arg missense NM_001407731.1:c.3762T>A NP_001394660.1:p.Ser1254Arg missense NM_001407732.1:c.3762T>A NP_001394661.1:p.Ser1254Arg missense NM_001407733.1:c.3762T>A NP_001394662.1:p.Ser1254Arg missense NM_001407734.1:c.3762T>A NP_001394663.1:p.Ser1254Arg missense NM_001407735.1:c.3762T>A NP_001394664.1:p.Ser1254Arg missense NM_001407736.1:c.3762T>A NP_001394665.1:p.Ser1254Arg missense NM_001407737.1:c.3762T>A NP_001394666.1:p.Ser1254Arg missense NM_001407738.1:c.3762T>A NP_001394667.1:p.Ser1254Arg missense NM_001407739.1:c.3762T>A NP_001394668.1:p.Ser1254Arg missense NM_001407740.1:c.3759T>A NP_001394669.1:p.Ser1253Arg missense NM_001407741.1:c.3759T>A NP_001394670.1:p.Ser1253Arg missense NM_001407742.1:c.3759T>A NP_001394671.1:p.Ser1253Arg missense NM_001407743.1:c.3759T>A NP_001394672.1:p.Ser1253Arg missense NM_001407744.1:c.3759T>A NP_001394673.1:p.Ser1253Arg missense NM_001407745.1:c.3759T>A NP_001394674.1:p.Ser1253Arg missense NM_001407746.1:c.3759T>A NP_001394675.1:p.Ser1253Arg missense NM_001407747.1:c.3759T>A NP_001394676.1:p.Ser1253Arg missense NM_001407748.1:c.3759T>A NP_001394677.1:p.Ser1253Arg missense NM_001407749.1:c.3759T>A NP_001394678.1:p.Ser1253Arg missense NM_001407750.1:c.3762T>A NP_001394679.1:p.Ser1254Arg missense NM_001407751.1:c.3762T>A NP_001394680.1:p.Ser1254Arg missense NM_001407752.1:c.3762T>A NP_001394681.1:p.Ser1254Arg missense NM_001407838.1:c.3759T>A NP_001394767.1:p.Ser1253Arg missense NM_001407839.1:c.3759T>A NP_001394768.1:p.Ser1253Arg missense NM_001407841.1:c.3759T>A NP_001394770.1:p.Ser1253Arg missense NM_001407842.1:c.3759T>A NP_001394771.1:p.Ser1253Arg missense NM_001407843.1:c.3759T>A NP_001394772.1:p.Ser1253Arg missense NM_001407844.1:c.3759T>A NP_001394773.1:p.Ser1253Arg missense NM_001407845.1:c.3759T>A NP_001394774.1:p.Ser1253Arg missense NM_001407846.1:c.3759T>A NP_001394775.1:p.Ser1253Arg missense NM_001407847.1:c.3759T>A NP_001394776.1:p.Ser1253Arg missense NM_001407848.1:c.3759T>A NP_001394777.1:p.Ser1253Arg missense NM_001407849.1:c.3759T>A NP_001394778.1:p.Ser1253Arg missense NM_001407850.1:c.3762T>A NP_001394779.1:p.Ser1254Arg missense NM_001407851.1:c.3762T>A NP_001394780.1:p.Ser1254Arg missense NM_001407852.1:c.3762T>A NP_001394781.1:p.Ser1254Arg missense NM_001407853.1:c.3690T>A NP_001394782.1:p.Ser1230Arg missense NM_001407854.1:c.3903T>A NP_001394783.1:p.Ser1301Arg missense NM_001407858.1:c.3903T>A NP_001394787.1:p.Ser1301Arg missense NM_001407859.1:c.3903T>A NP_001394788.1:p.Ser1301Arg missense NM_001407860.1:c.3900T>A NP_001394789.1:p.Ser1300Arg missense NM_001407861.1:c.3900T>A NP_001394790.1:p.Ser1300Arg missense NM_001407862.1:c.3702T>A NP_001394791.1:p.Ser1234Arg missense NM_001407863.1:c.3780T>A NP_001394792.1:p.Ser1260Arg missense NM_001407874.1:c.3699T>A NP_001394803.1:p.Ser1233Arg missense NM_001407875.1:c.3699T>A NP_001394804.1:p.Ser1233Arg missense NM_001407879.1:c.3693T>A NP_001394808.1:p.Ser1231Arg missense NM_001407881.1:c.3693T>A NP_001394810.1:p.Ser1231Arg missense NM_001407882.1:c.3693T>A NP_001394811.1:p.Ser1231Arg missense NM_001407884.1:c.3693T>A NP_001394813.1:p.Ser1231Arg missense NM_001407885.1:c.3693T>A NP_001394814.1:p.Ser1231Arg missense NM_001407886.1:c.3693T>A NP_001394815.1:p.Ser1231Arg missense NM_001407887.1:c.3693T>A NP_001394816.1:p.Ser1231Arg missense NM_001407889.1:c.3693T>A NP_001394818.1:p.Ser1231Arg missense NM_001407894.1:c.3690T>A NP_001394823.1:p.Ser1230Arg missense NM_001407895.1:c.3690T>A NP_001394824.1:p.Ser1230Arg missense NM_001407896.1:c.3690T>A NP_001394825.1:p.Ser1230Arg missense NM_001407897.1:c.3690T>A NP_001394826.1:p.Ser1230Arg missense NM_001407898.1:c.3690T>A NP_001394827.1:p.Ser1230Arg missense NM_001407899.1:c.3690T>A NP_001394828.1:p.Ser1230Arg missense NM_001407900.1:c.3693T>A NP_001394829.1:p.Ser1231Arg missense NM_001407902.1:c.3693T>A NP_001394831.1:p.Ser1231Arg missense NM_001407904.1:c.3693T>A NP_001394833.1:p.Ser1231Arg missense NM_001407906.1:c.3693T>A NP_001394835.1:p.Ser1231Arg missense NM_001407907.1:c.3693T>A NP_001394836.1:p.Ser1231Arg missense NM_001407908.1:c.3693T>A NP_001394837.1:p.Ser1231Arg missense NM_001407909.1:c.3693T>A NP_001394838.1:p.Ser1231Arg missense NM_001407910.1:c.3693T>A NP_001394839.1:p.Ser1231Arg missense NM_001407915.1:c.3690T>A NP_001394844.1:p.Ser1230Arg missense NM_001407916.1:c.3690T>A NP_001394845.1:p.Ser1230Arg missense NM_001407917.1:c.3690T>A NP_001394846.1:p.Ser1230Arg missense NM_001407918.1:c.3690T>A NP_001394847.1:p.Ser1230Arg missense NM_001407919.1:c.3780T>A NP_001394848.1:p.Ser1260Arg missense NM_001407920.1:c.3639T>A NP_001394849.1:p.Ser1213Arg missense NM_001407921.1:c.3639T>A NP_001394850.1:p.Ser1213Arg missense NM_001407922.1:c.3639T>A NP_001394851.1:p.Ser1213Arg missense NM_001407923.1:c.3639T>A NP_001394852.1:p.Ser1213Arg missense NM_001407924.1:c.3639T>A NP_001394853.1:p.Ser1213Arg missense NM_001407925.1:c.3639T>A NP_001394854.1:p.Ser1213Arg missense NM_001407926.1:c.3639T>A NP_001394855.1:p.Ser1213Arg missense NM_001407927.1:c.3639T>A NP_001394856.1:p.Ser1213Arg missense NM_001407928.1:c.3639T>A NP_001394857.1:p.Ser1213Arg missense NM_001407929.1:c.3639T>A NP_001394858.1:p.Ser1213Arg missense NM_001407930.1:c.3636T>A NP_001394859.1:p.Ser1212Arg missense NM_001407931.1:c.3636T>A NP_001394860.1:p.Ser1212Arg missense NM_001407932.1:c.3636T>A NP_001394861.1:p.Ser1212Arg missense NM_001407933.1:c.3639T>A NP_001394862.1:p.Ser1213Arg missense NM_001407934.1:c.3636T>A NP_001394863.1:p.Ser1212Arg missense NM_001407935.1:c.3639T>A NP_001394864.1:p.Ser1213Arg missense NM_001407936.1:c.3636T>A NP_001394865.1:p.Ser1212Arg missense NM_001407937.1:c.3780T>A NP_001394866.1:p.Ser1260Arg missense NM_001407938.1:c.3780T>A NP_001394867.1:p.Ser1260Arg missense NM_001407939.1:c.3780T>A NP_001394868.1:p.Ser1260Arg missense NM_001407940.1:c.3777T>A NP_001394869.1:p.Ser1259Arg missense NM_001407941.1:c.3777T>A NP_001394870.1:p.Ser1259Arg missense NM_001407942.1:c.3762T>A NP_001394871.1:p.Ser1254Arg missense NM_001407943.1:c.3759T>A NP_001394872.1:p.Ser1253Arg missense NM_001407944.1:c.3762T>A NP_001394873.1:p.Ser1254Arg missense NM_001407945.1:c.3762T>A NP_001394874.1:p.Ser1254Arg missense NM_001407946.1:c.3570T>A NP_001394875.1:p.Ser1190Arg missense NM_001407947.1:c.3570T>A NP_001394876.1:p.Ser1190Arg missense NM_001407948.1:c.3570T>A NP_001394877.1:p.Ser1190Arg missense NM_001407949.1:c.3570T>A NP_001394878.1:p.Ser1190Arg missense NM_001407950.1:c.3570T>A NP_001394879.1:p.Ser1190Arg missense NM_001407951.1:c.3570T>A NP_001394880.1:p.Ser1190Arg missense NM_001407952.1:c.3570T>A NP_001394881.1:p.Ser1190Arg missense NM_001407953.1:c.3570T>A NP_001394882.1:p.Ser1190Arg missense NM_001407954.1:c.3567T>A NP_001394883.1:p.Ser1189Arg missense NM_001407955.1:c.3567T>A NP_001394884.1:p.Ser1189Arg missense NM_001407956.1:c.3567T>A NP_001394885.1:p.Ser1189Arg missense NM_001407957.1:c.3570T>A NP_001394886.1:p.Ser1190Arg missense NM_001407958.1:c.3567T>A NP_001394887.1:p.Ser1189Arg missense NM_001407959.1:c.3522T>A NP_001394888.1:p.Ser1174Arg missense NM_001407960.1:c.3522T>A NP_001394889.1:p.Ser1174Arg missense NM_001407962.1:c.3519T>A NP_001394891.1:p.Ser1173Arg missense NM_001407963.1:c.3522T>A NP_001394892.1:p.Ser1174Arg missense NM_001407964.1:c.3759T>A NP_001394893.1:p.Ser1253Arg missense NM_001407965.1:c.3399T>A NP_001394894.1:p.Ser1133Arg missense NM_001407966.1:c.3015T>A NP_001394895.1:p.Ser1005Arg missense NM_001407967.1:c.3015T>A NP_001394896.1:p.Ser1005Arg missense NM_001407968.1:c.1299T>A NP_001394897.1:p.Ser433Arg missense NM_001407969.1:c.1299T>A NP_001394898.1:p.Ser433Arg missense NM_001407970.1:c.788-596T>A intron variant NM_001407971.1:c.788-596T>A intron variant NM_001407972.1:c.785-596T>A intron variant NM_001407973.1:c.788-596T>A intron variant NM_001407974.1:c.788-596T>A intron variant NM_001407975.1:c.788-596T>A intron variant NM_001407976.1:c.788-596T>A intron variant NM_001407977.1:c.788-596T>A intron variant NM_001407978.1:c.788-596T>A intron variant NM_001407979.1:c.788-596T>A intron variant NM_001407980.1:c.788-596T>A intron variant NM_001407981.1:c.788-596T>A intron variant NM_001407982.1:c.788-596T>A intron variant NM_001407983.1:c.788-596T>A intron variant NM_001407984.1:c.785-596T>A intron variant NM_001407985.1:c.785-596T>A intron variant NM_001407986.1:c.785-596T>A intron variant NM_001407990.1:c.788-596T>A intron variant NM_001407991.1:c.785-596T>A intron variant NM_001407992.1:c.785-596T>A intron variant NM_001407993.1:c.788-596T>A intron variant NM_001408392.1:c.785-596T>A intron variant NM_001408396.1:c.785-596T>A intron variant NM_001408397.1:c.785-596T>A intron variant NM_001408398.1:c.785-596T>A intron variant NM_001408399.1:c.785-596T>A intron variant NM_001408400.1:c.785-596T>A intron variant NM_001408401.1:c.785-596T>A intron variant NM_001408402.1:c.785-596T>A intron variant NM_001408403.1:c.788-596T>A intron variant NM_001408404.1:c.788-596T>A intron variant NM_001408406.1:c.791-605T>A intron variant NM_001408407.1:c.785-596T>A intron variant NM_001408408.1:c.779-596T>A intron variant NM_001408409.1:c.710-596T>A intron variant NM_001408410.1:c.647-596T>A intron variant NM_001408411.1:c.710-596T>A intron variant NM_001408412.1:c.710-596T>A intron variant NM_001408413.1:c.707-596T>A intron variant NM_001408414.1:c.710-596T>A intron variant NM_001408415.1:c.710-596T>A intron variant NM_001408416.1:c.707-596T>A intron variant NM_001408418.1:c.671-596T>A intron variant NM_001408419.1:c.671-596T>A intron variant NM_001408420.1:c.671-596T>A intron variant NM_001408421.1:c.668-596T>A intron variant NM_001408422.1:c.671-596T>A intron variant NM_001408423.1:c.671-596T>A intron variant NM_001408424.1:c.668-596T>A intron variant NM_001408425.1:c.665-596T>A intron variant NM_001408426.1:c.665-596T>A intron variant NM_001408427.1:c.665-596T>A intron variant NM_001408428.1:c.665-596T>A intron variant NM_001408429.1:c.665-596T>A intron variant NM_001408430.1:c.665-596T>A intron variant NM_001408431.1:c.668-596T>A intron variant NM_001408432.1:c.662-596T>A intron variant NM_001408433.1:c.662-596T>A intron variant NM_001408434.1:c.662-596T>A intron variant NM_001408435.1:c.662-596T>A intron variant NM_001408436.1:c.665-596T>A intron variant NM_001408437.1:c.665-596T>A intron variant NM_001408438.1:c.665-596T>A intron variant NM_001408439.1:c.665-596T>A intron variant NM_001408440.1:c.665-596T>A intron variant NM_001408441.1:c.665-596T>A intron variant NM_001408442.1:c.665-596T>A intron variant NM_001408443.1:c.665-596T>A intron variant NM_001408444.1:c.665-596T>A intron variant NM_001408445.1:c.662-596T>A intron variant NM_001408446.1:c.662-596T>A intron variant NM_001408447.1:c.662-596T>A intron variant NM_001408448.1:c.662-596T>A intron variant NM_001408450.1:c.662-596T>A intron variant NM_001408451.1:c.653-596T>A intron variant NM_001408452.1:c.647-596T>A intron variant NM_001408453.1:c.647-596T>A intron variant NM_001408454.1:c.647-596T>A intron variant NM_001408455.1:c.647-596T>A intron variant NM_001408456.1:c.647-596T>A intron variant NM_001408457.1:c.647-596T>A intron variant NM_001408458.1:c.647-596T>A intron variant NM_001408459.1:c.647-596T>A intron variant NM_001408460.1:c.647-596T>A intron variant NM_001408461.1:c.647-596T>A intron variant NM_001408462.1:c.644-596T>A intron variant NM_001408463.1:c.644-596T>A intron variant NM_001408464.1:c.644-596T>A intron variant NM_001408465.1:c.644-596T>A intron variant NM_001408466.1:c.647-596T>A intron variant NM_001408467.1:c.647-596T>A intron variant NM_001408468.1:c.644-596T>A intron variant NM_001408469.1:c.647-596T>A intron variant NM_001408470.1:c.644-596T>A intron variant NM_001408472.1:c.788-596T>A intron variant NM_001408473.1:c.785-596T>A intron variant NM_001408474.1:c.587-596T>A intron variant NM_001408475.1:c.584-596T>A intron variant NM_001408476.1:c.587-596T>A intron variant NM_001408478.1:c.578-596T>A intron variant NM_001408479.1:c.578-596T>A intron variant NM_001408480.1:c.578-596T>A intron variant NM_001408481.1:c.578-596T>A intron variant NM_001408482.1:c.578-596T>A intron variant NM_001408483.1:c.578-596T>A intron variant NM_001408484.1:c.578-596T>A intron variant NM_001408485.1:c.578-596T>A intron variant NM_001408489.1:c.578-596T>A intron variant NM_001408490.1:c.575-596T>A intron variant NM_001408491.1:c.575-596T>A intron variant NM_001408492.1:c.578-596T>A intron variant NM_001408493.1:c.575-596T>A intron variant NM_001408494.1:c.548-596T>A intron variant NM_001408495.1:c.545-596T>A intron variant NM_001408496.1:c.524-596T>A intron variant NM_001408497.1:c.524-596T>A intron variant NM_001408498.1:c.524-596T>A intron variant NM_001408499.1:c.524-596T>A intron variant NM_001408500.1:c.524-596T>A intron variant NM_001408501.1:c.524-596T>A intron variant NM_001408502.1:c.455-596T>A intron variant NM_001408503.1:c.521-596T>A intron variant NM_001408504.1:c.521-596T>A intron variant NM_001408505.1:c.521-596T>A intron variant NM_001408506.1:c.461-596T>A intron variant NM_001408507.1:c.461-596T>A intron variant NM_001408508.1:c.452-596T>A intron variant NM_001408509.1:c.452-596T>A intron variant NM_001408510.1:c.407-596T>A intron variant NM_001408511.1:c.404-596T>A intron variant NM_001408512.1:c.284-596T>A intron variant NM_001408513.1:c.578-596T>A intron variant NM_001408514.1:c.578-596T>A intron variant NM_007297.4:c.3762T>A NP_009228.2:p.Ser1254Arg missense NM_007298.4:c.788-596T>A intron variant NM_007299.4:c.788-596T>A intron variant NM_007300.4:c.3903T>A NP_009231.2:p.Ser1301Arg missense NR_027676.1:n.4039T>A NC_000017.11:g.43091628A>T NC_000017.10:g.41243645A>T NG_005905.2:g.126356T>A NG_087068.1:g.610A>T LRG_292:g.126356T>A LRG_292t1:c.3903T>A LRG_292p1:p.Ser1301Arg P38398:p.Ser1301Arg U14680.1:n.4022T>A - Protein change
- S1301R, S1254R, S1190R, S1234R, S1253R, S1274R, S1174R, S1005R, S1259R, S1233R, S1275R, S1298R, S433R, S1189R, S1213R, S1230R, S1231R, S1260R, S1300R, S1133R, S1173R, S1212R
- Other names
-
4022T>A
- Canonical SPDI
- NC_000017.11:43091627:A:T
-
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 |
13040 | 14846 | |
| 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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Aug 27, 2020 | RCV000048374.8 | |
| Uncertain significance (2) |
no assertion criteria provided
|
Oct 19, 2011 | RCV000077559.5 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Feb 26, 2024 | RCV000775152.10 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Aug 27, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076387.7
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
In summary, this variant is a rare missense change that is not expected to affect protein function. There is no indication that it causes disease, … (more)
In summary, this variant is a rare missense change that is not expected to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not affect BRCA1 protein function. In BRCA1-null embryonic stem cells, this missense variant was able to restore the proliferation defect of these cells, similar to the wild-type BRCA1 protein (PMID: 23867111). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 55044). This sequence change replaces serine with arginine at codon 1301 of the BRCA1 protein (p.Ser1301Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. (less)
|
|
|
Uncertain significance
(Feb 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002620968.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.S1301R variant (also known as c.3903T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide … (more)
The p.S1301R variant (also known as c.3903T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide position 3903. The serine at codon 1301 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Apr 18, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000909287.2
First in ClinVar: May 20, 2019 Last updated: Jun 22, 2020 |
|
|
|
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: SCV003849483.1
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
(Apr 21, 2011)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000109361.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
|
|
|
Uncertain significance
(Oct 19, 2011)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
somatic
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144913.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Western European
|
Comment:
Comment:
The p.S1301R variant (also known as c.3903T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide position 3903. The serine at codon 1301 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
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, this variant is a rare missense change that is not expected to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not affect BRCA1 protein function. In BRCA1-null embryonic stem cells, this missense variant was able to restore the proliferation defect of these cells, similar to the wild-type BRCA1 protein (PMID: 23867111). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 55044). This sequence change replaces serine with arginine at codon 1301 of the BRCA1 protein (p.Ser1301Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine.
Comment:
The p.S1301R variant (also known as c.3903T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide position 3903. The serine at codon 1301 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
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 |
| A high-throughput functional complementation assay for classification of BRCA1 missense variants. | Bouwman P | Cancer discovery | 2013 | PMID: 23867111 |
| The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Text-mined citations for rs273900719 ...
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 Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.