Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012566 | SCV001173035 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-13 | criteria provided, single submitter | clinical testing | The p.R550K variant (also known as c.1649G>A), located in coding exon 11 of the CDH1 gene, results from a G to A substitution at nucleotide position 1649. The arginine at codon 550 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001221320 | SCV001393360 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-10-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 550 of the CDH1 protein (p.Arg550Lys). 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. ClinVar contains an entry for this variant (Variation ID: 819744). 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 disruptive. 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. |
| Gene |
RCV002462257 | SCV002757405 | uncertain significance | not provided | 2022-05-23 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235021, 22850631) |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002462257 | SCV004220799 | uncertain significance | not provided | 2023-08-09 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Baylor Genetics | RCV004569902 | SCV005060129 | uncertain significance | Familial cancer of breast | 2023-11-28 | criteria provided, single submitter | clinical testing |