Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003040198 | SCV003348334 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-04-21 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 16 of the CDH1 protein (p.Gln16Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. |
Ambry Genetics | RCV004603277 | SCV005095368 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-24 | criteria provided, single submitter | clinical testing | The p.Q16R variant (also known as c.47A>G), located in coding exon 1 of the CDH1 gene, results from an A to G substitution at nucleotide position 47. The glutamine at codon 16 is replaced by arginine, an amino acid with highly similar 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. Based on the available evidence, the clinical significance of this variant remains unclear. |