ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1670A>G (p.Lys557Arg)

dbSNP: rs1173188736
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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 RCV001325857 SCV001516866 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-05-10 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1025529). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 557 of the CDH1 protein (p.Lys557Arg).
GeneDx RCV001773651 SCV002004520 uncertain significance not provided 2023-05-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter 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, 33237286)
Ambry Genetics RCV002395720 SCV002703074 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-28 criteria provided, single submitter clinical testing The p.K557R variant (also known as c.1670A>G), located in coding exon 11 of the CDH1 gene, results from an A to G substitution at nucleotide position 1670. The lysine at codon 557 is replaced by arginine, an amino acid with highly similar 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.

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