ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2574C>G (p.Asp858Glu)

dbSNP: rs1060501245
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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 RCV000704728 SCV000833688 uncertain significance Hereditary diffuse gastric adenocarcinoma 2019-05-15 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CDH1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 858 of the CDH1 protein (p.Asp858Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid.
Color Diagnostics, LLC DBA Color Health RCV001805821 SCV002053586 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 858 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.
Ambry Genetics RCV001805821 SCV002743082 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-19 criteria provided, single submitter clinical testing The p.D858E variant (also known as c.2574C>G), located in coding exon 16 of the CDH1 gene, results from a C to G substitution at nucleotide position 2574. The aspartic acid at codon 858 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003460981 SCV004215625 uncertain significance Familial cancer of breast 2023-10-06 criteria provided, single submitter clinical testing

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