ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1837G>T (p.Val613Leu) (rs200124136)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235100 SCV000209693 uncertain significance not provided 2018-12-31 criteria provided, single submitter clinical testing This variant is denoted ATM c.1837G>T at the cDNA level and p.Val613Leu (V613L) at the protein level, and results in the change of a Valine to a Leucine (GTG>TTG). ATM Val613Leu has been previously reported in at least two individuals with breast cancer and one with a glioma, but has also been observed in a control individual (Tavtigian 2009, Lu 2015, Caminsky 2016, Tiao 2017). ATM Val613Leu was not observed at a significant 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 Val613Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000159687 SCV000216139 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000205987 SCV000259499 uncertain significance Ataxia-telangiectasia syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 613 of the ATM protein (p.Val613Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs200124136, ExAC 0.009%). This variant has been reported in an individual affected with breast cancer (PMID: 19781682). ClinVar contains an entry for this variant (Variation ID: 181922). 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.
Color RCV000159687 SCV000682004 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-24 criteria provided, single submitter clinical testing

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