ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1342C>G (p.Gln448Glu)

gnomAD frequency: 0.00002  dbSNP: rs1421067964
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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 RCV000639223 SCV000760793 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-03-04 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with CDH1-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 532450). This variant is present in population databases (no rsID available, gnomAD 0.008%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 448 of the CDH1 protein (p.Gln448Glu).
Ambry Genetics RCV001010966 SCV001171236 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-24 criteria provided, single submitter clinical testing The p.Q448E variant (also known as c.1342C>G), located in coding exon 10 of the CDH1 gene, results from a C to G substitution at nucleotide position 1342. The glutamine at codon 448 is replaced by glutamic acid, 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.
GeneDx RCV003235321 SCV003933093 uncertain significance not provided 2022-12-13 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)
Baylor Genetics RCV004568407 SCV005060142 uncertain significance Familial cancer of breast 2023-11-16 criteria provided, single submitter clinical testing

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