ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3254T>C (p.Val1085Ala)

dbSNP: rs1284116426
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001040904 SCV001204495 uncertain significance Ataxia-telangiectasia syndrome 2021-08-13 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 1085 of the ATM protein (p.Val1085Ala). The valine residue is highly 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 ATM-related conditions. 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 disruptive, but 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.
Color Diagnostics, LLC DBA Color Health RCV001186416 SCV001352818 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-09 criteria provided, single submitter clinical testing This missense variant replaces valine with alanine at codon 1085 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001186416 SCV002612446 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-30 criteria provided, single submitter clinical testing The p.V1085A variant (also known as c.3254T>C), located in coding exon 21 of the ATM gene, results from a T to C substitution at nucleotide position 3254. The valine at codon 1085 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003467726 SCV004210289 uncertain significance Familial cancer of breast 2023-06-08 criteria provided, single submitter clinical testing

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.