Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328453 | SCV001365460 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.1312delA p.(Thr438fs) 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 |
RCV000657359 | SCV000779091 | likely pathogenic | not provided | 2017-07-21 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in CDH1 is denoted c.1312delA at the cDNA level and p.Thr438GlnfsX17 (T438QfsX17) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAAA[delA]CAGC. The deletion causes a frameshift which changes a Threonine to a Glutamine at codon 438, and creates a premature stop codon at position 17 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available evidence, we consider this deletion to be a likely pathogenic variant. |
Myriad Genetics, |
RCV003336121 | SCV004043484 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-13 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |