ClinVar Miner

Submissions for variant NM_020631.5(PLEKHG5):c.2131C>G (p.Gln711Glu) (rs761272621)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585593 SCV000692599 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000585593 SCV000779620 uncertain significance not provided 2018-05-10 criteria provided, single submitter clinical testing The Q711E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q711E variant is not observed in large population cohorts (Lek et al., 2016). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Invitae RCV000645442 SCV000767187 uncertain significance Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c 2017-09-08 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 711 of the PLEKHG5 protein (p.Gln711Glu). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs761272621, ExAC 0.005%). This variant has not been reported in the literature in individuals with PLEKHG5-related disease. 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 glutamic acid 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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