Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV003328298 | SCV001142241 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.468G>A (p.Trp156Ter) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting. |
| Gene |
RCV000218005 | SCV000279544 | likely pathogenic | not provided | 2020-10-09 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV003298284 | SCV004007961 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-21 | criteria provided, single submitter | clinical testing | The p.W156* pathogenic mutation (also known as c.468G>A), located in coding exon 4 of the CDH1 gene, results from a G to A substitution at nucleotide position 468. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |