ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.554T>C (p.Val185Ala)

gnomAD frequency: 0.00001  dbSNP: rs730881335
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
GeneDx RCV000159676 SCV000209677 uncertain significance not provided 2014-09-30 criteria provided, single submitter clinical testing This variant is denoted ATM c.554T>C at the cDNA level, p.Val185Ala (V185A) at the protein level, and results in the change of a Valine to an Alanine (GTT>GCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val185Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Alanine share similar properties, this is considered a conservative amino acid substitution. ATM Val185Ala occurs at a position that is well conserved across species and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether ATM Val185Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000805180 SCV000945127 uncertain significance Ataxia-telangiectasia syndrome 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 185 of the ATM protein (p.Val185Ala). This variant is present in population databases (rs730881335, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 181912). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002345549 SCV002651760 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-24 criteria provided, single submitter clinical testing The p.V185A variant (also known as c.554T>C), located in coding exon 5 of the ATM gene, results from a T to C substitution at nucleotide position 554. The valine at codon 185 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004567190 SCV005057097 uncertain significance Familial cancer of breast 2024-01-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV000805180 SCV002094085 uncertain significance Ataxia-telangiectasia syndrome 2019-10-28 no assertion criteria provided 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.