Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489626 | SCV000577542 | uncertain significance | not provided | 2023-02-16 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Seen in individual with Charcot Marie Tooth disease; however, no further clinical information was available (Lupo et al., 2016); This variant is associated with the following publications: (PMID: 26752306) |
Invitae | RCV001051945 | SCV001216130 | uncertain significance | Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C | 2022-07-27 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 240 of the PLEKHG5 protein (p.Asp240Asn). This variant is present in population databases (rs765882140, gnomAD 0.01%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 26752306). ClinVar contains an entry for this variant (Variation ID: 426957). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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, |
RCV000489626 | SCV002541195 | uncertain significance | not provided | 2021-08-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002376895 | SCV002672308 | uncertain significance | Inborn genetic diseases | 2020-11-06 | criteria provided, single submitter | clinical testing | The p.D240N variant (also known as c.718G>A), located in coding exon 7 of the PLEKHG5 gene, results from a G to A substitution at nucleotide position 718. The aspartic acid at codon 240 is replaced by asparagine, an amino acid with highly similar properties. This variant was detected in an individual with Charcot-Marie-Tooth (CMT) disease; however, clinical details were limited (Lupo V et al. J Mol Diagn, 2016 Mar;18:225-34). This amino acid position is not well 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. |