ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1268G>A (p.Gly423Glu)

dbSNP: rs1064793300
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479779 SCV000565676 uncertain significance not provided 2023-07-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 19782031, 22419737)
Ambry Genetics RCV000574107 SCV000669273 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-10 criteria provided, single submitter clinical testing The p.G423E variant (also known as c.1268G>A), located in coding exon 11 of the CHEK2 gene, results from a G to A substitution at nucleotide position 1268. The glycine at codon 423 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Invitae RCV001856822 SCV002253186 uncertain significance Familial cancer of breast 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 423 of the CHEK2 protein (p.Gly423Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 418554). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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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