ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2202A>T (p.Arg734Ser)

gnomAD frequency: 0.00002  dbSNP: rs745717070
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538100 SCV000637779 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-11-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 734 of the CDH1 protein (p.Arg734Ser). This variant is present in population databases (rs745717070, 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: 463746). 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 disruptive. 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.
Ambry Genetics RCV000567522 SCV000666289 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-30 criteria provided, single submitter clinical testing The p.R734S variant (also known as c.2202A>T), located in coding exon 14 of the CDH1 gene, results from an A to T substitution at nucleotide position 2202. The arginine at codon 734 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not 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.
Color Diagnostics, LLC DBA Color Health RCV000567522 SCV001354017 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-18 criteria provided, single submitter clinical testing
GeneDx RCV001778996 SCV002015232 uncertain significance not provided 2021-11-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek 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; This variant is associated with the following publications: (PMID: 15235021, 22850631)
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268149 SCV002551791 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV003459228 SCV004215713 uncertain significance Familial cancer of breast 2023-06-16 criteria provided, single submitter clinical testing

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