ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs80356946
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047332 SCV000075345 likely benign Hereditary breast ovarian cancer syndrome 2023-12-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000216374 SCV000275880 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-08 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 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.
Color Diagnostics, LLC DBA Color Health RCV000216374 SCV000909389 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-29 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 361 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has reported that this variant does not impact BRCA1 function in a homology-directed repair assay and a cisplatin sensitivity assay performed in a Brca1-deficient mouse embryonic stem cells ( (PMID: 32546644). This variant has been reported in an individual affected with breast or ovarian cancer (PMID: 32438681), and reported in one multifactorial analysis with a family history likelihood ratio for pathogenicity of 0.2259 (PMID: 31131967). 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 likely benign not specified 2021-08-09 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 BRCA1, 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 was absent in 251080 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1081T>C has been reported in the literature in an individual affected with breast and/or ovarian cancer (Santonocito_2020). This report however, do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. Several multifactorial analysis studies report the variant as likely benign (example: Cline_2019, Bouwman_2020). Three other ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=1) or uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
University of Washington Department of Laboratory Medicine, University of Washington RCV000216374 SCV003846182 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Breast Cancer Information Core (BIC) (BRCA1) RCV000111542 SCV000144000 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2003-12-23 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000111542 SCV000297583 benign Breast-ovarian cancer, familial, susceptibility to, 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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