ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.79G>A (p.Val27Ile) (rs754770960)

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
Ambry Genetics RCV000165389 SCV000216116 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-13 criteria provided, single submitter clinical testing Insufficient evidence
GeneDx RCV000235556 SCV000294083 uncertain significance not provided 2016-03-14 criteria provided, single submitter clinical testing This variant is denoted ATM c.79G>A at the cDNA level, p.Val27Ile (V27I) at the protein level, and results in the change of a Valine to an Isoleucine (GTT>ATT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val27Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. ATM Val27Ile occurs at a position where amino acids with properties similar to Valine are tolerated across species and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether ATM Val27Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000467148 SCV000546975 uncertain significance Ataxia-telangiectasia syndrome 2019-11-18 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 27 of the ATM protein (p.Val27Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs754770960, ExAC 0.001%) but has not been reported in the literature in individuals with a ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 185887). 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 isoleucine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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.