ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4139T>C (p.Ile1380Thr)

dbSNP: rs2137503277
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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 RCV001877227 SCV002131551 uncertain significance Hereditary breast ovarian cancer syndrome 2021-07-28 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 1380 of the BRCA2 protein (p.Ile1380Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine.
University of Washington Department of Laboratory Medicine, University of Washington RCV003159036 SCV003848717 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 RCV003159036 SCV005551981 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-01 criteria provided, single submitter clinical testing The p.I1380T variant (also known as c.4139T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 4139. The isoleucine at codon 1380 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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