ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1432A>T (p.Thr478Ser)

dbSNP: rs2137471409
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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 RCV001925257 SCV002172425 uncertain significance Hereditary breast ovarian cancer syndrome 2021-01-11 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 478 of the BRCA2 protein (p.Thr478Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003156831 SCV003851383 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 RCV003156831 SCV005097571 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-05 criteria provided, single submitter clinical testing The p.T478S variant (also known as c.1432A>T), located in coding exon 9 of the BRCA2 gene, results from an A to T substitution at nucleotide position 1432. The threonine at codon 478 is replaced by serine, 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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