ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4329C>A (p.His1443Gln) (rs377065665)

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
Ambry Genetics RCV000164709 SCV000215377 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000164709 SCV000687541 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-12 criteria provided, single submitter clinical testing
GeneDx RCV000521912 SCV000616645 uncertain significance not provided 2017-10-06 criteria provided, single submitter clinical testing This variant is denoted ATM c.4329C>A at the cDNA level, p.His1443Gln (H1443Q) at the protein level,and results in the change of a Histidine to a Glutamine (CAC>CAA). This variant has not, to our knowledge, beenpublished in the literature as pathogenic or benign. ATM His1443Gln was not observed at a significant frequency inlarge population cohorts (Lek 2016). Since Histidine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM His1443Gln occurs at a position that is conserved across species and is notlocated in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have onprotein structure and function. Based on currently available evidence, it is unclear whether ATM His1443Gln is apathogenic or benign variant. We consider it to be a variant of uncertain significance
Illumina Clinical Services Laboratory,Illumina RCV000307354 SCV000367053 uncertain significance Ataxia-telangiectasia syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000307354 SCV000546709 uncertain significance Ataxia-telangiectasia syndrome 2018-11-15 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 1443 of the ATM protein (p.His1443Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. This variant is present in population databases (rs377065665, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 185311). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.