ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.2713C>T (p.Leu905Phe)

gnomAD frequency: 0.00001  dbSNP: rs774696513
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545725 SCV000646043 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 905 of the PLEKHG5 protein (p.Leu905Phe). This variant is present in population databases (rs774696513, gnomAD 0.01%). 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: 468911). 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: "Tolerated"; PolyPhen-2: "Possibly 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 RCV002431643 SCV002744243 uncertain significance Inborn genetic diseases 2021-01-05 criteria provided, single submitter clinical testing The p.L905F variant (also known as c.2713C>T), located in coding exon 19 of the PLEKHG5 gene, results from a C to T substitution at nucleotide position 2713. The leucine at codon 905 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, phenylalanine is the reference amino acid in other 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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