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
Invitae RCV000196544 SCV000254091 uncertain significance Ataxia-telangiectasia syndrome 2019-08-29 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). This variant has not been reported in the literature in individuals with 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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 RCV000215921 SCV000276086 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-20 criteria provided, single submitter clinical testing Insufficient evidence
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.
Counsyl RCV000196544 SCV000799202 uncertain significance Ataxia-telangiectasia syndrome 2018-04-12 criteria provided, single submitter clinical testing
Color RCV000215921 SCV000913930 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-05 criteria provided, single submitter clinical testing

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