Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000221471 | SCV000275561 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-07 | criteria provided, single submitter | clinical testing | The p.V611D variant (also known as c.1832T>A), located in coding exon 12 of the CDH1 gene, results from a T to A substitution at nucleotide position 1832. The valine at codon 611 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is poorly 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 |
RCV001853555 | SCV002293471 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 611 of the CDH1 protein (p.Val611Asp). This variant is present in population databases (rs779351070, gnomAD 0.0009%). 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: 231651). 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 tolerated. 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. |
| Baylor Genetics | RCV003462472 | SCV004215718 | uncertain significance | Familial cancer of breast | 2023-06-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004719767 | SCV005326028 | uncertain significance | not provided | 2023-12-01 | 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: 27978560, 15235021, 22850631) |