ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3505G>A (p.Glu1169Lys) (rs200765255)

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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 RCV000166372 SCV000217162 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-09 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000204598 SCV000260878 uncertain significance Ataxia-telangiectasia syndrome 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1169 of the ATM protein (p.Glu1169Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs200765255, ExAC 0.001%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 186729). 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 disruptive, 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.
GeneDx RCV000413647 SCV000490414 uncertain significance not provided 2018-03-30 criteria provided, single submitter clinical testing This variant is denoted ATM c.3505G>A at the cDNA level, p.Glu1169Lys (E1169K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). This variant has been reported in at least one individual with an unspecified cancer (Mandelker 2017). ATM Glu1169Lys was not observed at a significant frequency in large population cohorts (Lek 2016). ATM Glu1169Lys is located in the beta-adaptin interaction domain (Tavtigian 2009). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether ATM Glu1169Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000166372 SCV000687484 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-03 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000413647 SCV000805540 uncertain significance not provided 2017-10-20 criteria provided, single submitter clinical testing

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