Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV003328390 | SCV001437619 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-25 | reviewed by expert panel | curation | The c.1590dup (p.Asn531fs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://https://gnomad.broadinstitute.org/). This variant has been reported in a family meeting HDGC clinical criteria (PS4_Supporting, PMID: 10477433). 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. |
| Gene |
RCV000520434 | SCV000617357 | pathogenic | not provided | 2017-03-01 | criteria provided, single submitter | clinical testing | This duplication of one nucleotide in CDH1 is denoted c.1590dupC at the cDNA level and p.Asn531GlnfsX6 (N531QfsX6) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CTGC[dupC]AACT. The duplication causes a frameshift which changes an Asparagine to a Glutamine at codon 531, and creates a premature stop codon at position 6 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. CDH1 c.1590dupC, also known as 1588insC using alternate nomenclature, has been reported in a Hereditary Diffuse Gastric Cancer family (Guilford 1999). We consider this variant to be pathogenic. |
| Labcorp Genetics |
RCV001260576 | SCV002235966 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-04-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 449339). This premature translational stop signal has been observed in individual(s) with gastric cancer (PMID: 10477433). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn531Glnfs*6) 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). |
| Myriad Genetics, |
RCV001260576 | SCV004043531 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-14 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003464107 | SCV004215753 | pathogenic | Familial cancer of breast | 2023-01-19 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV004579550 | SCV000033275 | pathogenic | DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME | 2001-07-01 | no assertion criteria provided | literature only |