ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7195C>G (p.Gln2399Glu)

dbSNP: rs2085985186
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
Genetic Services Laboratory, University of Chicago RCV001820633 SCV002068067 uncertain significance not specified 2020-04-28 criteria provided, single submitter clinical testing DNA sequence analysis of the ATM gene demonstrated a sequence change, c.7195C>G, in exon 49 that results in an amino acid change, p.Gln2399Glu. This sequence change does not appear to have been previously described in patients with ATM-related disorders. This sequence change is a novel sequence change that has not been described in the population databases (ExAC and gnomAD). The p.Gln2399Glu change affects a highly conserved amino acid residue located in a domain of the ATM protein that is known to be functional. The p.Gln2399Glu substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these evidences and the lack of functional studies, the clinical significance of the p.Gln2399Glu change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869732 SCV002205105 uncertain significance Ataxia-telangiectasia syndrome 2021-01-31 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 2399 of the ATM protein (p.Gln2399Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Ambry Genetics RCV003355552 SCV004053945 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-03 criteria provided, single submitter clinical testing The p.Q2399E variant (also known as c.7195C>G), located in coding exon 48 of the ATM gene, results from a C to G substitution at nucleotide position 7195. The glutamine at codon 2399 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.