ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1516G>T (p.Gly506Cys) (rs587779816)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115143 SCV000215651 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000115143 SCV000537575 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515225 SCV000611344 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2017-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000211963 SCV000149052 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing This variant is denoted ATM c.1516G>T at the cDNA level, p.Gly506Cys (G506C) at the protein level, and results in the change of a Glycine to a Cysteine (GGC>TGC). This variant has been identified in at least one individual who underwent hereditary cancer panel testing (Yorczyk 2015), but also in a population based study of Qatari individuals not selected for personal medical history (Rodriguez-Flores 2014). ATM Gly506Cys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In-silico analyses, which includes protein predictors and evolutionary conservation, are inconsistent. Based on the currently available evidence, it is unclear whether ATM Gly506Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000168231 SCV000218900 uncertain significance Ataxia-telangiectasia syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 506 of the ATM protein (p.Gly506Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. This variant is present in population databases (rs587779816, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127339). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
Mendelics RCV000168231 SCV000838490 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 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.