Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000221624 | SCV000272996 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-31 | criteria provided, single submitter | clinical testing | The p.M517V variant (also known as c.1549A>G), located in coding exon 10 of the CDH1 gene, results from an A to G substitution at nucleotide position 1549. The methionine at codon 517 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. |
Labcorp Genetics |
RCV000794319 | SCV000933719 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2019-11-11 | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of hereditary diffuse gastric cancer (Invitae). ClinVar contains an entry for this variant (Variation ID: 229694). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 517 of the CDH1 protein (p.Met517Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. |