Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328280 | SCV001142239 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-29 | reviewed by expert panel | curation | The c.2293C>T (p.Gln765*) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). The variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000839094.1). In summary, 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting. |
Ambry Genetics | RCV000222740 | SCV000274004 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-03-10 | criteria provided, single submitter | clinical testing | The p.Q765* pathogenic mutation (also known as c.2293C>T), located in coding exon 14 of the CDH1 gene, results from a C to T substitution at nucleotide position 2293. This changes the amino acid from a glutamine to a stop codon within coding exon 14. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with hereditary diffuse gastric cancer (Ambry internal data). 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. |
Mendelics | RCV000709398 | SCV000839094 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000709398 | SCV004044932 | 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. |