ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2944C>T (p.Arg982Cys) (rs587779830)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563065 SCV000660575 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Color RCV000563065 SCV000682091 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-10 criteria provided, single submitter clinical testing
GeneDx RCV000115168 SCV000149077 uncertain significance not provided 2017-04-04 criteria provided, single submitter clinical testing This variant is denoted ATM c.2944C>T at the cDNA level, p.Arg982Cys (R982C) at the protein level, and results in the change of an Arginine to a Cysteine (CGT>TGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Arg982Cys was not observed at a significant frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Arg982Cys occurs at a position that is conserved across species and is located in the beta-adaptin interaction domain (Tavtigian 2009). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether ATM Arg982Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000465835 SCV000546989 uncertain significance Ataxia-telangiectasia syndrome 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 982 of the ATM protein (p.Arg982Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs587779830, ExAC 0.003%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127363). 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.
Mendelics RCV000465835 SCV000838515 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing

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