ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3695C>G (p.Ser1232Cys) (rs367603277)

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
GeneDx RCV000236770 SCV000293850 uncertain significance not provided 2016-01-20 criteria provided, single submitter clinical testing This variant is denoted ATM c.3695C>G at the cDNA level, p.Ser1232Cys (S1232C) at the protein level, and results in the change of a Serine to a Cysteine (TCT>TGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Ser1232Cys was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Serine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Ser1232Cys occurs at a position that is not conserved and is located in the beta-adaptin interaction domain (Tavtigian 2009). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether ATM Ser1232Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000543894 SCV000622441 uncertain significance Ataxia-telangiectasia syndrome 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 1232 of the ATM protein (p.Ser1232Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 246339). 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, this variant has uncertain impact on ATM function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000571286 SCV000667970 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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.