ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.134C>G (p.Thr45Arg)

dbSNP: rs558321010
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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 RCV001011025 SCV001171302 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-31 criteria provided, single submitter clinical testing The p.T45R variant (also known as c.134C>G), located in coding exon 1 of the CHEK2 gene, results from a C to G substitution at nucleotide position 134. The threonine at codon 45 is replaced by arginine, an amino acid with similar 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.
PreventionGenetics, part of Exact Sciences RCV003396595 SCV004112429 uncertain significance CHEK2-related condition 2023-02-20 criteria provided, single submitter clinical testing The CHEK2 c.134C>G variant is predicted to result in the amino acid substitution p.Thr45Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/818927/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Invitae RCV003500617 SCV004338187 uncertain significance Familial cancer of breast 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 45 of the CHEK2 protein (p.Thr45Arg). 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: 818927). 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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