ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.513C>G (p.Tyr171Ter) (rs786201693)

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 RCV000164103 SCV000214716 pathogenic Hereditary cancer-predisposing syndrome 2014-04-03 criteria provided, single submitter clinical testing
Counsyl RCV000533506 SCV000795016 likely pathogenic Ataxia-telangiectasia syndrome 2017-10-24 criteria provided, single submitter clinical testing
GeneDx RCV000520700 SCV000617363 pathogenic not provided 2018-12-13 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.513C>G at the cDNA level and p.Tyr171Ter (Y171X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAG) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in the homozygous state in a patient with ataxia-telangiectasia whose lymphoblastoid cell line expressed no ATM protein and has also been observed in at least one individual referred for hereditary cancer testing (Keimling 2011, LaDuca 2017). We consider ATM Tyr171Ter to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000533506 SCV000694299 pathogenic Ataxia-telangiectasia syndrome 2016-09-29 criteria provided, single submitter clinical testing Variant summary: The ATM c.513C>G (p.Tyr171X) variant results in a premature termination codon, predicted to cause a truncated or absent ATM protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Arg2506fsX3, p.Lys2756X). Mutation taster predicts a damaging outcome for this variant. This variant was absent in 43866 control chromosomes while it was found in at least one AT patient in homozygosity, indicating causality. In addition, a study reported ATM to be undetected in LCLs derived from an AT patient carying the variant of interest in homozygosity; these LCLs also had deregulated SSA and HDR, and were deficient in phosphorylation of SMC1, KAP1, and Chk2, further supporting pathogenicity. Moreover, a clinical diagnostic laboratory classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000533506 SCV000622567 pathogenic Ataxia-telangiectasia syndrome 2018-07-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr171*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with ataxia telangiectasia (PMID: 9887333). ClinVar contains an entry for this variant (Variation ID: 184787). Experimental studies have shown that this nonsense change disrupts ATM protein function (PMID: 21778326). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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.