ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.383C>T (p.Pro128Leu)

gnomAD frequency: 0.00001  dbSNP: rs587781879
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130206 SCV000185044 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-29 criteria provided, single submitter clinical testing The p.P128L variant (also known as c.383C>T), located in coding exon 2 of the CHEK2 gene, results from a C to T substitution at nucleotide position 383. The proline at codon 128 is replaced by leucine, 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.
Invitae RCV000227657 SCV000289684 uncertain significance Familial cancer of breast 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 128 of the CHEK2 protein (p.Pro128Leu). 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: 141613). 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 tolerated. 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.
Color Diagnostics, LLC DBA Color Health RCV000130206 SCV000684634 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-31 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 128 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study has shown this variant protein does not impact protein localization or kinase activity (PMID: 37449874). In a large breast cancer case-control meta analysis conducted by the ENIGMA consortium, this variant was reported in 3/73048 cases and 1/88658 unaffected controls (PMID: 37449874). 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.

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.