ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2954A>T (p.Asp985Val) (rs864622159)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205414 SCV000259506 uncertain significance Ataxia-telangiectasia syndrome 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 985 of the ATM protein (p.Asp985Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 219567). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
GeneDx RCV000486669 SCV000569302 uncertain significance not provided 2017-09-14 criteria provided, single submitter clinical testing This variant is denoted ATM c.2954A>T at the cDNA level, p.Asp985Val (D985V) at the protein level, and results in the change of an Aspartic Acid to a Valine (GAT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Asp985Val was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Aspartic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Asp985Val occurs at a position where amino acids with properties similar to Aspartic Acid are tolerated across species and is located within 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 Asp985Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565728 SCV000665470 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000565728 SCV000682094 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-17 criteria provided, single submitter clinical testing

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