ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.280C>G (p.Arg94Gly) (rs119103263)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091326 SCV001247285 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing
Invitae RCV001206471 SCV001377780 pathogenic Charcot-Marie-Tooth disease, type 2 2019-08-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 94 of the MFN2 protein (p.Arg94Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease (PMID: 21508331). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg94 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15064763, 16437557, 16714318, 17215403, 20418531, 24862862). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789702 SCV000929078 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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