ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1483A>G (p.Ile495Val) (rs786201969)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164527 SCV000215181 uncertain significance Hereditary cancer-predisposing syndrome 2014-05-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589044 SCV000694185 uncertain significance not provided 2017-07-06 criteria provided, single submitter clinical testing Variant summary: The ATM c.1483A>G (p.Ile495Val) variant causes a missense change involving the alteration of a conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). The variant of interest has not been found in a large, broad control population, ExAC in 121308 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor 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).
Invitae RCV000627916 SCV000748800 uncertain significance Ataxia-telangiectasia syndrome 2017-09-07 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 495 of the ATM protein (p.Ile495Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 185158). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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