Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000481386 | SCV000564835 | uncertain significance | not provided | 2015-02-02 | criteria provided, single submitter | clinical testing | This variant is denoted CDH1 c.1034T>C at the cDNA level, p.Val345Ala (V345A) at the protein level, and results in the change of a Valine to an Alanine (GTT>GCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CDH1 Val345Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Alanine share similar properties, this is considered a conservative amino acid substitution. CDH1 Val345Ala occurs at a position that is highly conserved across species and is located in the Cadherin 2 domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether CDH1 Val345Ala is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Labcorp Genetics |
RCV000805145 | SCV000945090 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 345 of the CDH1 protein (p.Val345Ala). 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: 418112). 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 | RCV004023104 | SCV005022138 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-08 | criteria provided, single submitter | clinical testing | The p.V345A variant (also known as c.1034T>C), located in coding exon 8 of the CDH1 gene, results from a T to C substitution at nucleotide position 1034. The valine at codon 345 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |