ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1317G>T (p.Gln439His)

gnomAD frequency: 0.00001  dbSNP: rs878854915
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226245 SCV000289661 uncertain significance Familial cancer of breast 2023-10-10 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 439 of the CHEK2 protein (p.Gln439His). 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: 240737). 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.
Ambry Genetics RCV000561448 SCV000666391 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-18 criteria provided, single submitter clinical testing The p.Q439H variant (also known as c.1317G>T), located in coding exon 11 of the CHEK2 gene, results from a G to T substitution at nucleotide position 1317. The glutamine at codon 439 is replaced by histidine, an amino acid with highly 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.
Counsyl RCV000226245 SCV000785245 uncertain significance Familial cancer of breast 2017-06-13 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000561448 SCV001360203 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-05 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 439 of the CHEK2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Myriad Genetics, Inc. RCV000226245 SCV004020133 uncertain significance Familial cancer of breast 2023-03-08 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.