ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1889T>C (p.Val630Ala) (rs587782226)

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 RCV000130917 SCV000185827 uncertain significance Hereditary cancer-predisposing syndrome 2013-11-24 criteria provided, single submitter clinical testing
GeneDx RCV000235574 SCV000293187 uncertain significance not provided 2018-02-05 criteria provided, single submitter clinical testing This variant is denoted ATM c.1889T>C at the cDNA level, p.Val630Ala (V630A) at the protein level, and results in the change of a Valine to an Alanine (GTG>GCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val630Ala was not observed at a significant allele frequency in large population cohorts (Lek 2016). ATM Val630Ala 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 Val630Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000553410 SCV000622290 uncertain significance Ataxia-telangiectasia syndrome 2017-11-07 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 630 of the ATM protein (p.Val630Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine 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 a ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 142090). 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 alanine 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, 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.

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.