ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4306A>G (p.Ile1436Val)

dbSNP: rs778282885
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000772747 SCV000906080 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-28 criteria provided, single submitter clinical testing
Mendelics RCV000989028 SCV001139088 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001217070 SCV001388897 uncertain significance Hereditary breast ovarian cancer syndrome 2023-08-07 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 628306). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs778282885, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1436 of the BRCA2 protein (p.Ile1436Val).
University of Washington Department of Laboratory Medicine, University of Washington RCV000772747 SCV003850400 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 RCV000772747 SCV003853782 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-27 criteria provided, single submitter clinical testing The p.I1436V variant (also known as c.4306A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4306. The isoleucine at codon 1436 is replaced by valine, an amino acid with highly 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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