ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1468G>A (p.Glu490Lys)

dbSNP: rs1555516147
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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 RCV000539873 SCV000637725 uncertain significance Hereditary diffuse gastric adenocarcinoma 2020-07-14 criteria provided, single submitter clinical testing In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This sequence change replaces glutamic acid with lysine at codon 490 of the CDH1 protein (p.Glu490Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CDH1-related disease.
Ambry Genetics RCV000565014 SCV000666309 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-30 criteria provided, single submitter clinical testing The p.E490K variant (also known as c.1468G>A), located in coding exon 10 of the CDH1 gene, results from a G to A substitution at nucleotide position 1468. The glutamic acid at codon 490 is replaced by lysine, an amino acid with similar properties. This alteration was detected in 1/5589 German BRCA1/2-negative probands with breast cancer (Hauke J et al. Cancer Med, 2018 04;7:1349-1358). 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.
Mendelics RCV000539873 SCV000839088 uncertain significance Hereditary diffuse gastric adenocarcinoma 2018-07-02 criteria provided, single submitter clinical testing

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