ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4880A>T (p.Gln1627Leu) (rs786203857)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167347 SCV000218199 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-03 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000167347 SCV000904616 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779772 SCV000916562 uncertain significance not specified 2018-01-02 criteria provided, single submitter clinical testing Variant summary: The ATM c.4880A>T (p.Gln1627Leu) variant involves the alteration of a conserved nucleotide and is predicted to be damaging by 4/4 in silico tools (SNPsandGO not captured due to low reliability index). This variant is absent in 246170 control chromosomes (gnomAD). One clinical diagnostic laboratory has classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV001056090 SCV001220510 uncertain significance Ataxia-telangiectasia syndrome 2019-12-06 criteria provided, single submitter clinical testing This sequence change replaces glutamine with leucine at codon 1627 of the ATM protein (p.Gln1627Leu). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 187603). 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.

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