ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.1360C>T (p.Arg454Cys)

gnomAD frequency: 0.00001  dbSNP: rs200086651
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000819278 SCV000959928 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2022-05-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 454 of the PLEKHG5 protein (p.Arg454Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 661784). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002381856 SCV002699621 uncertain significance Inborn genetic diseases 2020-10-20 criteria provided, single submitter clinical testing The p.R454C variant (also known as c.1360C>T), located in coding exon 12 of the PLEKHG5 gene, results from a C to T substitution at nucleotide position 1360. The arginine at codon 454 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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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