ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1547T>C (p.Leu516Ser)

dbSNP: rs786202195
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164896 SCV000215583 likely pathogenic Hereditary cancer-predisposing syndrome 2023-04-21 criteria provided, single submitter clinical testing The p.L516S variant (also known as c.1547T>C), located in coding exon 9 of the ATM gene, results from a T to C substitution at nucleotide position 1547. The leucine at codon 516 is replaced by serine, an amino acid with dissimilar properties. This alteration was identified in cis with ATM c.1514T>C (p.F505S) in four children from a consanguineous Arabic family with a mild presentation of Ataxia Telangiectasia, each of whose parents were found to be heterozygous for this haplotype. This same report also found that cells from these children showed reduced, but not absent, ATM protein expression as well as reduced and delayed phosphorylation of KAP1 (an ATM substrate) after neocarzinostatin-induced DNA damage (Bielorai B et al. Pediatr Hematol Oncol, 2013 Sep;30:574-82). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001349973 SCV001544343 uncertain significance Ataxia-telangiectasia syndrome 2023-09-01 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 185468). 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. 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 disruptive. This missense change has been observed in individual(s) with clinical features of ataxia telangiectasia and malignant peritoneal mesothelioma (PMID: 23509889, 30124550). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 516 of the ATM protein (p.Leu516Ser).

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.