ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1198G>T (p.Gly400Trp)

gnomAD frequency: 0.00001  dbSNP: rs1342820782
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519455 SCV000617073 uncertain significance not provided 2021-04-26 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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
Color Diagnostics, LLC DBA Color Health RCV000777112 SCV000912799 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000777112 SCV001170418 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-13 criteria provided, single submitter clinical testing The p.G400W variant (also known as c.1198G>T), located in coding exon 10 of the CHEK2 gene, results from a G to T substitution at nucleotide position 1198. The glycine at codon 400 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is well 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.
Invitae RCV001240305 SCV001413238 uncertain significance Familial cancer of breast 2023-11-02 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 400 of the CHEK2 protein (p.Gly400Trp). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 449214). 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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