ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1675A>T (p.Ser559Cys)

dbSNP: rs1555516566
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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 RCV000538831 SCV000637742 uncertain significance Hereditary diffuse gastric adenocarcinoma 2018-05-14 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 559 of the CDH1 protein (p.Ser559Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDH1-related disease. ClinVar contains an entry for this variant (Variation ID: 463726). 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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 RCV001178547 SCV001343012 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 559 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 not been identified 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.
PreventionGenetics, part of Exact Sciences RCV004722890 SCV005339154 uncertain significance CDH1-related disorder 2024-04-30 no assertion criteria provided clinical testing The CDH1 c.1675A>T variant is predicted to result in the amino acid substitution p.Ser559Cys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/463726/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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