Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017189 | SCV001178228 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-07 | criteria provided, single submitter | clinical testing | The p.S36C variant (also known as c.106A>T), located in coding exon 2 of the CDH1 gene, results from an A to T substitution at nucleotide position 106. The serine at codon 36 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is 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 |
RCV001070932 | SCV001236212 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-03-31 | 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 serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 36 of the CDH1 protein (p.Ser36Cys). ClinVar contains an entry for this variant (Variation ID: 822106). 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. |