ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.718G>A (p.Asp240Asn)

gnomAD frequency: 0.00007  dbSNP: rs765882140
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Mayo Clinic 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.

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