ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3978C>A (p.Asn1326Lys) (rs778123057)

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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 RCV000165616 SCV000216352 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-08 criteria provided, single submitter clinical testing
Invitae RCV000472893 SCV000547036 uncertain significance Ataxia-telangiectasia syndrome 2018-10-03 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 1326 of the ATM protein (p.Asn1326Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs778123057, 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: 186087). 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.
GeneDx RCV000481947 SCV000566255 uncertain significance not provided 2017-12-19 criteria provided, single submitter clinical testing This variant is denoted ATM c.3978C>A at the cDNA level, p.Asn1326Lys (N1326K) at the protein level, and results in the change of an Asparagine to a Lysine (AAC>AAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Asn1326Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Asparagine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Asn1326Lys 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 Asn1326Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance
PreventionGenetics,PreventionGenetics RCV000481947 SCV000805545 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing
Mendelics RCV000472893 SCV000838530 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing

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