ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1081T>C (p.Ser361Pro) (rs80356946)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047332 SCV000075345 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000216374 SCV000275880 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-18 criteria provided, single submitter clinical testing The p.S361P variant (also known as c.1081T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 1081. The serine at codon 361 is replaced by proline, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species, and proline is the reference amino acid in other 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.
Color Health, Inc RCV000216374 SCV000909389 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-31 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 361 of the BRCA1 protein. Computational programs predict the variant would have benign impact on protein structure and function. Serine at this position is poorly conserved, and variant proline is tolerated in more than ten mammalian species, suggesting that this variant may be tolerated for BRCA1 function (UCSC genome browser). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast and/or ovarian cancer (PMID: 32438681). This variant has been identified in 1/31396 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779861 SCV000916726 uncertain significance not specified 2018-03-07 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1081T>C (p.Ser361Pro) results in a non-conservative amino acid change located in the serine-rich domain (IPR025994) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 30970 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, c.1081T>C has not been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111542 SCV000144000 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000111542 SCV000297583 benign Breast-ovarian cancer, familial 1 2010-02-13 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357142 SCV001552510 uncertain significance not provided no assertion criteria provided clinical testing

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