ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2480A>G (p.Lys827Arg) (rs372230498)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197770 SCV000254069 uncertain significance Ataxia-telangiectasia syndrome 2018-08-23 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 827 of the ATM protein (p.Lys827Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs372230498, ExAC 0.01%). This variant has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 216194). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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, this variant has uncertain impact on ATM function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000218054 SCV000273121 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneKor MSA RCV000218054 SCV000821839 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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