ClinVar Miner

Submissions for variant NM_020631.5(PLEKHG5):c.2525G>A (p.Arg842Gln) (rs149682441)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725435 SCV000292872 uncertain significance not provided 2017-12-05 criteria provided, single submitter clinical testing The R842Q variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R842Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved across species and Glutamine is observed at this position in other species. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725435 SCV000336905 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing
Invitae RCV000645430 SCV000767175 uncertain significance Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 842 of the PLEKHG5 protein (p.Arg842Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs149682441, ExAC 0.03%). This variant has not been reported in the literature in individuals with PLEKHG5-related disease. ClinVar contains an entry for this variant (Variation ID: 245769). 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 glutamine 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. 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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