Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001210698 | SCV001382197 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 431 of the CDH1 protein (p.Asn431Lys). This variant is present in population databases (rs767350265, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 940999). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Ambry Genetics | RCV004033802 | SCV005022326 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-16 | criteria provided, single submitter | clinical testing | The p.N431K variant (also known as c.1293C>G), located in coding exon 9 of the CDH1 gene, results from a C to G substitution at nucleotide position 1293. The asparagine at codon 431 is replaced by lysine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |