ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3035G>C (p.Arg1012Thr)

dbSNP: rs876658464
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001047117 SCV001211052 uncertain significance Hereditary breast ovarian cancer syndrome 2022-05-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 1012 of the BRCA1 protein (p.Arg1012Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 844302). 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. 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.
Ambry Genetics RCV002436576 SCV002753198 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-27 criteria provided, single submitter clinical testing The p.R1012T variant (also known as c.3035G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 3035. The arginine at codon 1012 is replaced by threonine, 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002436576 SCV003849175 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).

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