Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328392 | SCV001365455 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.1031_1032dupTG p.(Val345fs) 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 |
RCV000523842 | SCV000618394 | likely pathogenic | not provided | 2017-10-18 | criteria provided, single submitter | clinical testing | This duplication of two nucleotides in CDH1 is denoted c.1031_1032dupTG at the cDNA level and p.Val345TrpfsX12 (V345WfsX12) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is CTGG[dupTG]GTTC. The duplication causes a frameshift which changes a Valine to a Tryptophan at codon 345, and creates a premature stop codon at position 12 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 information, we consider this duplication to be a likely pathogenic variant. |