ClinVar Miner

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

dbSNP: rs80357020
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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 RCV000561114 SCV000661045 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-09 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 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.
Invitae RCV000637599 SCV000759065 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1014 of the BRCA1 protein (p.Met1014Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 29907814). ClinVar contains an entry for this variant (Variation ID: 91604). 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 with a negative predictive value of 95%. 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 Diagnostics, LLC DBA Color Health RCV000561114 SCV000908928 likely benign Hereditary cancer-predisposing syndrome 2016-02-23 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000561114 SCV003849167 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).
Sharing Clinical Reports Project (SCRP) RCV000077121 SCV000108918 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2012-04-05 no assertion criteria provided clinical testing

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