ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.1280T>C (p.Met427Thr)

gnomAD frequency: 0.00002  dbSNP: rs754678569
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814924 SCV000955362 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2022-07-15 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 427 of the PLEKHG5 protein (p.Met427Thr). This variant is present in population databases (rs754678569, gnomAD 0.004%). 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: 658159). 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 threonine 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.
GeneDx RCV001772110 SCV002003521 uncertain significance not provided 2020-10-16 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Mayo Clinic Laboratories, Mayo Clinic RCV001772110 SCV004227736 uncertain significance not provided 2022-07-22 criteria provided, single submitter clinical testing BP4, PM2

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