ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.614T>C (p.Phe205Ser)

dbSNP: rs1567504835
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328467 SCV000864592 uncertain significance CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-21 reviewed by expert panel curation The c.614T>C (p. Phe205Ser) variant is absent in the gnomAD cohort (PM2_Supporting). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; internal laboratory contributor). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PM2_Supporting, PS4_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000736289 SCV001218516 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-01-26 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 599654). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 205 of the CDH1 protein (p.Phe205Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.

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