ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3041T>C (p.Met1014Thr) (rs80357020)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561114 SCV000661045 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-21 criteria provided, single submitter clinical testing The p.M1014T variant (also known as c.3041T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 3041. The methionine at codon 1014 is replaced by threonine, an amino acid with similar properties. In one study, this alteration was reported in 1/649 Brazilian patients who underwent genetic testing (Palmero EI et al. Sci Rep, 2018 Jun;8:9188). 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 RCV000637599 SCV000759065 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-09-09 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1014 of the BRCA1 protein (p.Met1014Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with personal or family history of breast and/or ovarian cancer (PMID: 29907814). ClinVar contains an entry for this variant (Variation ID: 91604). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Health, Inc RCV000561114 SCV000908928 likely benign Hereditary cancer-predisposing syndrome 2016-02-23 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077121 SCV000108918 uncertain significance Breast-ovarian cancer, familial 1 2012-04-05 no assertion criteria provided clinical testing

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