ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.221G>T (p.Arg74Leu)

dbSNP: rs761562625
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000639229 SCV000760799 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-12-07 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 532452). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 74 of the CDH1 protein (p.Arg74Leu).
Ambry Genetics RCV001014835 SCV001175597 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-30 criteria provided, single submitter clinical testing The p.R74L variant (also known as c.221G>T), located in coding exon 3 of the CDH1 gene, results from a G to T substitution at nucleotide position 221. The arginine at codon 74 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001756061 SCV002006909 uncertain significance not provided 2020-03-06 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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