Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV003328309 | SCV001244363 | uncertain significance | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-21 | reviewed by expert panel | curation | The CDH1 c.5G>T (p.Gly2Val) variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). To our knowledge, this variant has not been reported in the literature. In summary, this variant meets criteria to be classified as a variant of uncertain significance based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PM2_Supporting. |
| Labcorp Genetics |
RCV000231609 | SCV000288489 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-06-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the CDH1 protein (p.Gly2Val). 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: 239909). 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. 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. |
| Ambry Genetics | RCV002354656 | SCV002656167 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-04 | criteria provided, single submitter | clinical testing | The p.G2V variant (also known as c.5G>T), located in coding exon 1 of the CDH1 gene, results from a G to T substitution at nucleotide position 5. The glycine at codon 2 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is highly 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. |
| Gene |
RCV003126644 | SCV003803305 | uncertain significance | not provided | 2022-08-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Color Diagnostics, |
RCV002354656 | SCV004360419 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-07 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with valine at codon 2 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CDH1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |