ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.2127T>A (p.Asp709Glu)

gnomAD frequency: 0.00001  dbSNP: rs910994587
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001362904 SCV001558957 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 709 of the PLEKHG5 protein (p.Asp709Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. 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 glutamic acid 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.
Ambry Genetics RCV002550032 SCV003665385 uncertain significance Inborn genetic diseases 2022-11-17 criteria provided, single submitter clinical testing The c.2127T>A (p.D709E) alteration is located in exon 19 (coding exon 18) of the PLEKHG5 gene. This alteration results from a T to A substitution at nucleotide position 2127, causing the aspartic acid (D) at amino acid position 709 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect - Invitae Patient Insights Network RCV001362904 SCV001749880 not provided Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 09-02-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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