ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7196C>T (p.Thr2399Ile)

gnomAD frequency: 0.00001  dbSNP: rs786202614
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165508 SCV000216240 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-03 criteria provided, single submitter clinical testing The p.T2399I variant (also known as c.7196C>T), located in coding exon 13 of the BRCA2 gene, results from a C to T substitution at nucleotide position 7196. The threonine at codon 2399 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002515151 SCV002982591 uncertain significance Hereditary breast ovarian cancer syndrome 2023-10-11 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 2399 of the BRCA2 protein (p.Thr2399Ile). 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. ClinVar contains an entry for this variant (Variation ID: 185991). 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.
GeneDx RCV004589773 SCV005079864 uncertain significance not provided 2024-04-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Also known as 7424C>T; This variant is associated with the following publications: (PMID: 31131967, 32377563, 31853058, 29884841)

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