ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.400G>A (p.Glu134Lys)

gnomAD frequency: 0.00001  dbSNP: rs768676402
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065589 SCV001230555 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 134 of the PLEKHG5 protein (p.Glu134Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs768676402, ExAC 0.01%). 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 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 RCV003160541 SCV003890544 uncertain significance Inborn genetic diseases 2023-02-08 criteria provided, single submitter clinical testing The c.400G>A (p.E134K) alteration is located in exon 6 (coding exon 5) of the PLEKHG5 gene. This alteration results from a G to A substitution at nucleotide position 400, causing the glutamic acid (E) at amino acid position 134 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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