ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3149C>T (p.Thr1050Ile)

dbSNP: rs1010143466
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543517 SCV000635269 uncertain significance Hereditary breast ovarian cancer syndrome 2022-01-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 462287). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1050 of the BRCA2 protein (p.Thr1050Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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 BRCA2 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 RCV001018811 SCV001180090 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-21 criteria provided, single submitter clinical testing The p.T1050I variant (also known as c.3149C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 3149. The threonine at codon 1050 is replaced by isoleucine, 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 RCV001018811 SCV003851720 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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