ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.617T>C (p.Ile206Thr)

dbSNP: rs1254143781
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001218347 SCV001390227 uncertain significance Hereditary diffuse gastric adenocarcinoma 2019-05-07 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 206 of the CDH1 protein (p.Ile206Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine.
GeneDx RCV001586060 SCV001811905 uncertain significance not provided 2019-08-07 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; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002356930 SCV002655003 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-16 criteria provided, single submitter clinical testing The p.I206T variant (also known as c.617T>C), located in coding exon 5 of the CDH1 gene, results from a T to C substitution at nucleotide position 617. The isoleucine at codon 206 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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 RCV002356930 SCV004360454 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 206 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251202 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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