ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3449G>C (p.Arg1150Thr) (rs555219189)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115177 SCV000149086 uncertain significance not provided 2016-04-20 criteria provided, single submitter clinical testing This variant is denoted ATM c.3449G>C at the cDNA level, p.Arg1150Thr (R1150T) at the protein level, and results in the change of an Arginine to a Threonine (AGA>ACA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Arg1150Thr was not observed at a significant allele frequency in 1000 Genomes. Since Arginine and Threonine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Arg1150Thr occurs at a position that is conserved across species and is located in the beta-adaptin interaction region (Tavtigian 2009). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM Arg1150Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000199179 SCV000254084 uncertain significance Ataxia-telangiectasia syndrome 2018-08-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 1150 of the ATM protein (p.Arg1150Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs555219189, ExAC 0.1%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127372). 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.
Ambry Genetics RCV000215488 SCV000278041 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000215488 SCV000687480 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-17 criteria provided, single submitter clinical testing

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