ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8481T>G (p.Phe2827Leu) (rs886047614)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000294087 SCV000367070 uncertain significance Ataxia-telangiectasia syndrome 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573046 SCV000668102 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Invitae RCV000294087 SCV000823343 uncertain significance Ataxia-telangiectasia syndrome 2018-03-19 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 2827 of the ATM protein (p.Phe2827Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine 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 disease. ClinVar contains an entry for this variant (Variation ID: 302254). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). A different missense substitution at this codon (p.Phe2827Cys) has been determined to be pathogenic (PMID: 8755918, 19431188, 25040471, 9000145). This suggests that the phenylalanine residue is critical for ATM protein function and that other missense substitutions at this position may also be pathogenic. 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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