ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5069A>G (p.His1690Arg) (rs863224574)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198468 SCV000254118 uncertain significance Ataxia-telangiectasia syndrome 2017-12-22 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 1690 of the ATM protein (p.His1690Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. 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: 216221). 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.
Ambry Genetics RCV000562140 SCV000660689 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000589674 SCV000694297 uncertain significance not provided 2016-10-06 criteria provided, single submitter clinical testing Variant summary: The ATM c.5069A>G (p.His1690Arg) variant involves the alteration of a conserved nucleotide. His1690 is located in the Armadillo-type fold domain, and 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was absent in 121368 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.

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