ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5062A>G (p.Ile1688Val) (rs766053182)

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
Invitae RCV000470295 SCV000547087 uncertain significance Ataxia-telangiectasia syndrome 2018-09-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1688 of the ATM protein (p.Ile1688Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs766053182, ExAC 0.001%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 407693). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
GeneDx RCV000481399 SCV000564643 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing This variant is denoted ATM c.5062A>G at the cDNA level, p.Ile1688Val (I1688V) at the protein level, and results in the change of an Isoleucine to a Valine (ATA>GTA). This variant has been observed in an individual with clear cell renal cell carcinoma (Yehia 2018). ATM Ile1688Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Ile1688Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000568598 SCV000667864 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-06 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000568598 SCV000904617 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779765 SCV000916548 uncertain significance not specified 2017-10-06 criteria provided, single submitter clinical testing Variant summary: The ATM c.5062A>G (p.Ile1688Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant. This variant was found in 1/245972 control chromosomes (gnomAD) at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS).

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.