ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1642A>G (p.Thr548Ala) (rs878853486)

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
Invitae RCV000230533 SCV000282876 uncertain significance Ataxia-telangiectasia syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 548 of the ATM protein (p.Thr548Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 236676). 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.
Ambry Genetics RCV000575956 SCV000665509 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-23 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV001174987 SCV001338479 uncertain significance not specified 2020-04-17 criteria provided, single submitter clinical testing Variant summary: ATM c.1642A>G (p.Thr548Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 273796 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1642A>G has been reported in the literature in at least one individual affected with Breast Cancer (Momozawa_2018). This report does not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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.