ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1300G>C (p.Gly434Arg)

gnomAD frequency: 0.00002  dbSNP: rs587781783
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130036 SCV000184862 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-21 criteria provided, single submitter clinical testing The p.G434R variant (also known as c.1300G>C), located in coding exon 9 of the CDH1 gene, results from a G to C substitution at nucleotide position 1300. The glycine at codon 434 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000197039 SCV000254810 uncertain significance Hereditary diffuse gastric adenocarcinoma 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 434 of the CDH1 protein (p.Gly434Arg). This variant is present in population databases (rs587781783, gnomAD 0.007%). This missense change has been observed in individual(s) with cancer (not specified) (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 141484). 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.
Color Diagnostics, LLC DBA Color Health RCV000130036 SCV000684350 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-16 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 434 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected gastric cancer (PMID: 36833207), as well as in individual(s) age 70 years or older without cancer (http://whi.color.com/variant/16-68847378-G-C). This variant has been identified in 1/31406 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.
Counsyl RCV000197039 SCV000785362 uncertain significance Hereditary diffuse gastric adenocarcinoma 2017-07-13 criteria provided, single submitter clinical testing
GeneDx RCV002281954 SCV002571573 uncertain significance not provided 2022-09-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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)
Myriad Genetics, Inc. RCV000197039 SCV004020000 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-03-06 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
PreventionGenetics, part of Exact Sciences RCV003415946 SCV004108559 uncertain significance CDH1-related disorder 2023-10-11 criteria provided, single submitter clinical testing The CDH1 c.1300G>C variant is predicted to result in the amino acid substitution p.Gly434Arg. This variant has been reported in an individual with breast cancer (Table S4, Bhai et al. 2021. PubMed ID: 34326862). This variant is reported in 0.0065% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-68847378-G-C). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/141484/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000130036 SCV005045477 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-22 criteria provided, single submitter clinical testing

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