ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.950C>T (p.Thr317Ile)

gnomAD frequency: 0.00001  dbSNP: rs1341473353
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000535822 SCV000635748 uncertain significance Hereditary breast ovarian cancer syndrome 2024-03-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 317 of the BRCA2 protein (p.Thr317Ile). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 462530). 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 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758977 SCV000887966 uncertain significance not provided 2017-10-19 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV003157679 SCV003848155 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).
Ambry Genetics RCV003157679 SCV003855497 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-23 criteria provided, single submitter clinical testing The p.T317I variant (also known as c.950C>T), located in coding exon 9 of the BRCA2 gene, results from a C to T substitution at nucleotide position 950. The threonine at codon 317 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.

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