Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130507 | SCV000185376 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-25 | criteria provided, single submitter | clinical testing | The p.A563S variant (also known as c.1687G>T), located in coding exon 11 of the CDH1 gene, results from a G to T substitution at nucleotide position 1687. The alanine at codon 563 is replaced by serine, an amino acid with 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV000212374 | SCV000210919 | uncertain significance | not provided | 2024-03-25 | 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; Observed in individual(s) with a family history of breast cancer (PMID: 36436516); This variant is associated with the following publications: (PMID: 15235021, 22850631, 36436516) |
Labcorp Genetics |
RCV000473796 | SCV000545407 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 563 of the CDH1 protein (p.Ala563Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with CDH1-related conditions (PMID: 36436516). ClinVar contains an entry for this variant (Variation ID: 141834). 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. |
Color Diagnostics, |
RCV000130507 | SCV000684375 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-05 | criteria provided, single submitter | clinical testing | |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000473796 | SCV003926830 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PM2 (PMID: 30311375) |