ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3802G>A (p.Val1268Met) (rs863224564)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215921 SCV000276086 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000215921 SCV000913930 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
Counsyl RCV000196544 SCV000799202 uncertain significance Ataxia-telangiectasia syndrome 2018-04-12 criteria provided, single submitter clinical testing
GeneDx RCV000483314 SCV000568179 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing This variant is denoted ATM c.3802G>A at the cDNA level, p.Val1268Met (V1268M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val1268Met 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 that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Val1268Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000196544 SCV000254091 uncertain significance Ataxia-telangiectasia syndrome 2016-07-21 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 1268 of the ATM protein (p.Val1268Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 216204). 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: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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