ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.363C>A (p.His121Gln)

gnomAD frequency: 0.00001  dbSNP: rs781427897
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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 RCV003328463 SCV001142217 uncertain significance CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-21 reviewed by expert panel curation The c.363C>A variant is <1/50,000 alleles (0.002%, 2/113,262 alleles) in the non-Finnish European gnomAD subpopulation (PM2_Supporting; http://gnomad.broadinstitute.org). No additional evidence met criteria for consideration. Therefore, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000706606 SCV000835669 uncertain significance Hereditary diffuse gastric adenocarcinoma 2018-02-04 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 glutamine 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. This variant is present in population databases (rs781427897, ExAC 0.003%). This sequence change replaces histidine with glutamine at codon 121 of the CDH1 protein (p.His121Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine.

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