ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3587C>A (p.Thr1196Lys)

dbSNP: rs80356944
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218622 SCV000276041 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-02 criteria provided, single submitter clinical testing The p.T1196K variant (also known as c.3587C>A and 3706C>A), located in coding exon 9 of the BRCA1 gene, results from a C to A substitution at nucleotide position 3587. The threonine at codon 1196 is replaced by lysine, an amino acid with some similar properties. This alteration has been reported as a variant of unknown significance based on mammalian conservation and chemical characteristics of the amino acid substitution (Burk-Herrick A et al. Mamm Genome. 2006 Mar; 17(3):257-70). This amino acid position is poorly 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.
Invitae RCV001301253 SCV001490417 uncertain significance Hereditary breast ovarian cancer syndrome 2022-07-05 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 54925). This missense change has been observed in individual(s) with a personal or family history of breast and/or ovarian cancer (PMID: 9333265). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 1196 of the BRCA1 protein (p.Thr1196Lys).
GeneDx RCV002460902 SCV002757597 uncertain significance not provided 2022-05-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 3706C>A
University of Washington Department of Laboratory Medicine, University of Washington RCV000218622 SCV003848348 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) RCV000112126 SCV000144798 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 1997-02-15 no assertion criteria provided clinical testing

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