Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563227 | SCV000665175 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-14 | criteria provided, single submitter | clinical testing | The p.N376S variant (also known as c.1127A>G), located in coding exon 8 of the CDH1 gene, results from an A to G substitution at nucleotide position 1127. The asparagine at codon 376 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not 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. |
| Color Diagnostics, |
RCV000563227 | SCV000912246 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-04-07 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 376 of the CDH1 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251466 chromosomes 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. |
| Labcorp Genetics |
RCV001302597 | SCV001491811 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 376 of the CDH1 protein (p.Asn376Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with CDH1-related conditions (PMID: 36436516). ClinVar contains an entry for this variant (Variation ID: 481060). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| European Reference Network on Genetic Tumour Risk Syndromes |
RCV001302597 | SCV003926730 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PM2; BS2_Supporting (PMID: 30311375) |
| Center for Genomic Medicine, |
RCV003320193 | SCV004024291 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004569140 | SCV005060123 | uncertain significance | Familial cancer of breast | 2023-12-08 | criteria provided, single submitter | clinical testing |