Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003041263 | SCV003443611 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2022-02-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with hereditary diffuse gastric cancer syndrome (PMID: 20471195). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly759*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV003041263 | SCV003926910 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PVS1; PS4_Supporting; PM2 (PMID: 30311375) |
Myriad Genetics, |
RCV003041263 | SCV004044497 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Baylor Genetics | RCV003459732 | SCV004215739 | pathogenic | Familial cancer of breast | 2023-05-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004070148 | SCV005022314 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-07 | criteria provided, single submitter | clinical testing | The p.G759* pathogenic mutation (also known as c.2275G>T), located in coding exon 14 of the CDH1 gene, results from a G to T substitution at nucleotide position 2275. This changes the amino acid from a glycine to a stop codon within coding exon 14. This mutation has been detected in an Iranian family containing multiple relatives diagnosed with diffuse gastric cancer (Ghaffari SR et al. Eur J Surg Oncol, 2010 Jun;36:559-62). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |