ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.638C>A (p.Pro213His)

dbSNP: rs1569149890
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001025208 SCV001187352 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-30 criteria provided, single submitter clinical testing The p.P213H variant (also known as c.638C>A), located in coding exon 4 of the CHEK2 gene, results from a C to A substitution at nucleotide position 638. The proline at codon 213 is replaced by histidine, an amino acid with similar properties. This alteration has been reported with a carrier frequency of 0 in 7051 unselected breast cancer patients and 0.00062 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is highly 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 RCV001070326 SCV001235548 uncertain significance Familial cancer of breast 2022-02-14 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 826374). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 213 of the CHEK2 protein (p.Pro213His). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").

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.