Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568473 | SCV000665336 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-04-10 | criteria provided, single submitter | clinical testing | The p.C603Y variant (also known as c.1808G>A), located in coding exon 12 of the CDH1 gene, results from a G to A substitution at nucleotide position 1808. The cysteine at codon 603 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001865738 | SCV002190745 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-04-06 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 481145). 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 cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 603 of the CDH1 protein (p.Cys603Tyr). |