ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.409G>C (p.Ala137Pro)

dbSNP: rs876658797
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223635 SCV000274502 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-18 criteria provided, single submitter clinical testing The p.A137P variant (also known as c.409G>C), located in coding exon 4 of the CDH1 gene, results from a G to C substitution at nucleotide position 409. The alanine at codon 137 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000466626 SCV000545403 uncertain significance Hereditary diffuse gastric adenocarcinoma 2021-03-14 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDH1-related disease. ClinVar contains an entry for this variant (Variation ID: 230828). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 137 of the CDH1 protein (p.Ala137Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline.
Color Diagnostics, LLC DBA Color Health RCV000223635 SCV000904893 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 137 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 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.

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