ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5489T>C (p.Met1830Thr) (rs145812395)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212029 SCV000149122 uncertain significance not provided 2019-01-04 criteria provided, single submitter clinical testing This variant is denoted ATM c.5489T>C at the cDNA level, p.Met1830Thr (M1830T) at the protein level, and results in the change of a Methionine to a Threonine (ATG>ACG). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. ATM Met1830Thr 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 Met1830Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115213 SCV000217197 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-30 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000167908 SCV000218556 uncertain significance Ataxia-telangiectasia syndrome 2019-12-09 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1830 of the ATM protein (p.Met1830Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs145812395, ExAC 0.02%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127408). 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: "Benign"; Align-GVGD: "Class C25"). 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.
Color RCV000115213 SCV000682267 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-10 criteria provided, single submitter clinical testing

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