ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2614C>A (p.Leu872Met)

gnomAD frequency: 0.00002  dbSNP: rs749203461
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562588 SCV000666314 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-18 criteria provided, single submitter clinical testing The p.L872M variant (also known as c.2614C>A), located in coding exon 16 of the CDH1 gene, results from a C to A substitution at nucleotide position 2614. The leucine at codon 872 is replaced by methionine, an amino acid with highly similar 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 RCV000816835 SCV000957361 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 872 of the CDH1 protein (p.Leu872Met). This variant is present in population databases (rs749203461, gnomAD 0.02%). 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: 481693). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000562588 SCV004361285 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-06 criteria provided, single submitter clinical testing This missense variant replaces leucine with methionine at codon 872 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 CDH1-related disorders in the literature. This variant has been identified in 5/251476 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.
Baylor Genetics RCV004569151 SCV005060128 uncertain significance Familial cancer of breast 2023-11-29 criteria provided, single submitter clinical testing

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