ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1024G>A (p.Gly342Ser) (rs730881705)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160457 SCV000216850 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000160457 SCV000684548 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-29 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765617 SCV000896942 uncertain significance Familial cancer of breast; Li-Fraumeni syndrome 2; Osteosarcoma; Malignant tumor of prostate 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000212444 SCV000211022 uncertain significance not provided 2018-09-11 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.1024G>A at the cDNA level, p.Gly342Ser (G342S) at the protein level, and results in the change of a Glycine to a Serine (GGT>AGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. CHEK2 Gly342Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). CHEK2 Gly342Ser is located in the kinase domain (Cai 2009, Roeb 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether CHEK2 Gly342Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000230102 SCV000289639 uncertain significance Familial cancer of breast 2018-08-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 342 of the CHEK2 protein (p.Gly342Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs730881705, ExAC 0.009%). This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 182457). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Mendelics RCV000230102 SCV000839469 uncertain significance Familial cancer of breast 2018-07-02 criteria provided, single submitter clinical testing

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