Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000725435 | SCV000292872 | uncertain significance | not provided | 2020-02-10 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Eurofins Ntd Llc |
RCV000725435 | SCV000336905 | uncertain significance | not provided | 2017-06-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000645430 | SCV000767175 | uncertain significance | Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 842 of the PLEKHG5 protein (p.Arg842Gln). This variant is present in population databases (rs149682441, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. 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, which suggests that this missense change does not adversely affect protein function. 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. |
Mayo Clinic Laboratories, |
RCV000725435 | SCV001713770 | uncertain significance | not provided | 2020-05-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002450725 | SCV002739237 | uncertain significance | Inborn genetic diseases | 2019-12-10 | criteria provided, single submitter | clinical testing | The p.R842Q variant (also known as c.2525G>A), located in coding exon 19 of the PLEKHG5 gene, results from a G to A substitution at nucleotide position 2525. The arginine at codon 842 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |