ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.9128A>G (p.Lys3043Arg) (rs867893961)

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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 RCV000573858 SCV000660760 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000573858 SCV000905064 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-16 criteria provided, single submitter clinical testing
GeneDx RCV000237056 SCV000293945 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing This variant is denoted ATM c.9128A>G at the cDNA level, p.Lys3043Arg (K3043R) at the protein level, and results in the change of a Lysine to an Arginine (AAA>AGA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. ATM Lys3043Arg was not observed in large population cohorts (Lek 2016). This variant is located in the FATC domain (Stracker 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Lys3043Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000534818 SCV000622888 uncertain significance Ataxia-telangiectasia syndrome 2018-12-17 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 3043 of the ATM protein (p.Lys3043Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. 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: 246403). 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 tolerated, 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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