ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.38G>A (p.Arg13His) (rs778201041)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168074 SCV000218728 uncertain significance Ataxia-telangiectasia syndrome 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 13 of the ATM protein (p.Arg13His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. 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: 188171). 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.
Ambry Genetics RCV000222429 SCV000276277 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence
GeneDx RCV000254698 SCV000322154 uncertain significance not provided 2018-10-02 criteria provided, single submitter clinical testing This variant is denoted ATM c.38G>A at the cDNA level, p.Arg13His (R13H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has been observed in at least three individuals with breast cancer (Decker 2017). ATM Arg13His was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether ATM Arg13His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000168074 SCV000792414 uncertain significance Ataxia-telangiectasia syndrome 2017-06-27 criteria provided, single submitter clinical testing

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