ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1160C>A (p.Thr387Asn)

dbSNP: rs587780168
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219618 SCV000275085 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-07 criteria provided, single submitter clinical testing The p.T387N variant (also known as c.1160C>A), located in coding exon 10 of the CHEK2 gene, results from a C to A substitution at nucleotide position 1160. The threonine at codon 387 is replaced by asparagine, an amino acid with similar properties. The Thr-387 residue is an autophosphorylation site located within the activation loop of the Chk2 kinase domain, and has been demonstrated to have a dependency on Chk2 kinase activity for phosphorylation (Wu X et al. Hum. Mutat. 2006 Aug;27(8):742-7; Schwarz JK et al. Mol. Cancer Res. 2003 Jun; 1(8):598-609). 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.
Invitae RCV000230901 SCV000289648 uncertain significance Familial cancer of breast 2023-08-25 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 231287). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 21348412). This variant is present in population databases (rs587780168, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 387 of the CHEK2 protein (p.Thr387Asn).
Color Diagnostics, LLC DBA Color Health RCV000219618 SCV000689634 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-17 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818527 SCV002064598 uncertain significance not specified 2019-06-25 criteria provided, single submitter clinical testing

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.