ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1475G>C (p.Arg492Thr)

dbSNP: rs587781286
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128970 SCV000172855 likely benign Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000212371 SCV000210914 uncertain significance not provided 2019-11-15 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in an individual undergoing hereditary cancer panel testing (Mauer 2014); This variant is associated with the following publications: (PMID: 24113346)
Labcorp Genetics (formerly Invitae), Labcorp RCV000167912 SCV000218560 uncertain significance Hereditary diffuse gastric adenocarcinoma 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 492 of the CDH1 protein (p.Arg492Thr). This variant is present in population databases (rs587781286, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 140798). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV000128970 SCV000908737 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing

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