Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013388 | SCV001173967 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-02 | criteria provided, single submitter | clinical testing | The p.A617V variant (also known as c.1850C>T), located in coding exon 12 of the CDH1 gene, results from a C to T substitution at nucleotide position 1850. The alanine at codon 617 is replaced by valine, an amino acid with similar properties. This amino acid position is poorly 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 |
RCV003624440 | SCV004427541 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-12-26 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 617 of the CDH1 protein (p.Ala617Val). ClinVar contains an entry for this variant (Variation ID: 820182). 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. 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. |