ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1433C>A (p.Thr478Lys)

dbSNP: rs431825282
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559197 SCV000635161 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 478 of the BRCA2 protein (p.Thr478Lys). 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: 96764). 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 with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV000763880 SCV000894815 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000772727 SCV000906024 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000772727 SCV001171889 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-04 criteria provided, single submitter clinical testing The p.T478K variant (also known as c.1433C>A), located in coding exon 9 of the BRCA2 gene, results from a C to A substitution at nucleotide position 1433. The threonine at codon 478 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly conserved. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000772727 SCV003851384 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).
Sharing Clinical Reports Project (SCRP) RCV000082885 SCV000114959 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2012-05-01 no assertion criteria provided clinical testing

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