ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2579A>T (p.Asp860Val) (rs761251711)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574247 SCV000660677 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000574247 SCV000904596 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV000479651 SCV000567485 uncertain significance not provided 2017-09-25 criteria provided, single submitter clinical testing This variant is denoted ATM c.2579A>T at the cDNA level, p.Asp860Val (D860V) 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 Asp860Val was not observed at a significant allele frequency in large population cohorts (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 Asp860Val occurs at a position where amino acids with properties similar to Aspartic Acid are tolerated across species and is not located in a known functional domain. 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 Asp860Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000232136 SCV000282905 uncertain significance Ataxia-telangiectasia syndrome 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 860 of the ATM protein (p.Asp860Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs761251711, ExAC 0.001%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 236692). 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.

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