ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3628A>G (p.Met1210Val) (rs138212452)

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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 RCV000129482 SCV000184252 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000129482 SCV000911383 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing
Counsyl RCV000529913 SCV000788484 uncertain significance Ataxia-telangiectasia syndrome 2017-01-17 criteria provided, single submitter clinical testing
GeneDx RCV000482081 SCV000564629 uncertain significance not provided 2018-03-29 criteria provided, single submitter clinical testing This variant is denoted ATM c.3628A>G at the cDNA level, p.Met1210Val (M1210V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant was observed in an individual with lung cancer (Lu 2015). ATM Met1210Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the beta-adaptin interaction domain (Tavtigian 2009). 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 Met1210Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000529913 SCV000622437 uncertain significance Ataxia-telangiectasia syndrome 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 1210 of the ATM protein (p.Met1210Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs138212452, ExAC 0.04%). This variant has been reported in the literature in an individual affected with lung adenocarcinoma (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 141117). 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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