ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.68G>A (p.Arg23Gln) (rs587779858)

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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 RCV000115234 SCV000215102 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000115234 SCV000682372 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-16 criteria provided, single submitter clinical testing
GeneDx RCV000211939 SCV000149143 uncertain significance not specified 2015-12-07 criteria provided, single submitter clinical testing This variant is denoted ATM c.68G>A at the cDNA level, p.Arg23Gln (R23Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). Although this variant has not, to our knowledge, been published in the literature as a germline variant, it was observed as a somatic variant in a colorectal tumor (Greenman 2007). ATM Arg23Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Arg23Gln occurs at a position that is not conserved across species and is not located in a known functional domain (Tavtigian 2009, Stracker 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on the currently available information, we consider ATM Arg23Gln to be a variant of uncertain significance.
Invitae RCV000230719 SCV000283028 uncertain significance Ataxia-telangiectasia syndrome 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 23 of the ATM protein (p.Arg23Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. 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: 127429). 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.

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