ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.686G>T (p.Gly229Val)

gnomAD frequency: 0.00001  dbSNP: rs778212685
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215617 SCV000273581 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-26 criteria provided, single submitter clinical testing The p.G229V variant (also known as c.686G>T), located in coding exon 5 of the CHEK2 gene, results from a G to T substitution at nucleotide position 686. The glycine at codon 229 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000231597 SCV000289700 uncertain significance Familial cancer of breast 2023-09-20 criteria provided, single submitter clinical testing 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: 230142). 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 229 of the CHEK2 protein (p.Gly229Val).
Color Diagnostics, LLC DBA Color Health RCV000215617 SCV002053694 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-14 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 229 of the CHEK2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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