ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1312del (p.Thr438fs)

dbSNP: rs1555515920
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel 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.
GeneDx 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, Inc. 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.

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