ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6217C>G (p.Leu2073Val) (rs767406075)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484102 SCV000564650 uncertain significance not provided 2018-01-15 criteria provided, single submitter clinical testing This variant is denoted ATM c.6217C>G at the cDNA level, p.Leu2073Val (L2073V) at the protein level, and results in the change of a Leucine to a Valine (CTC>GTC). This variant was identified in a single breast tumor; however, as peripheral blood lymphocytes were not available it is not known if ATM Leu2073Val was somatic or germline in the reported case (Knappskog 2012). ATM Leu2073Val was not observed in large population cohorts (Lek 2016). This variant is located in the FAT domain (Stracker 2013). 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 Leu2073Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000804328 SCV000944232 uncertain significance Ataxia-telangiectasia syndrome 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 2073 of the ATM protein (p.Leu2073Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs767406075, ExAC 0.006%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 418038). 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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