ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.446C>T (p.Thr149Ile)

dbSNP: rs1593886804
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001022531 SCV001184283 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-18 criteria provided, single submitter clinical testing The p.T149I variant (also known as c.446C>T), located in coding exon 4 of the BRCA2 gene, results from a C to T substitution at nucleotide position 446. The threonine at codon 149 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 RCV001368709 SCV001565117 uncertain significance Hereditary breast ovarian cancer syndrome 2020-07-20 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 been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 824913). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 149 of the BRCA2 protein (p.Thr149Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine.

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