ClinVar Miner

Submissions for variant NM_000489.5(ATRX):c.4031A>G (p.Lys1344Arg) (rs782556767)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000499926 SCV000593555 uncertain significance not specified 2015-09-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000624685 SCV000741397 uncertain significance Inborn genetic diseases 2016-03-31 criteria provided, single submitter clinical testing
Invitae RCV000692943 SCV000820794 uncertain significance Alpha thalassemia-X-linked intellectual disability syndrome 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 1344 of the ATRX protein (p.Lys1344Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs782556767, ExAC 0.02%). This variant has not been reported in the literature in individuals with ATRX-related disease. ClinVar contains an entry for this variant (Variation ID: 434465). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; 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, 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.
GeneDx RCV000833627 SCV000975391 likely benign not provided 2019-02-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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