ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.1946G>A (p.Arg649His)

gnomAD frequency: 0.00001  dbSNP: rs763492075
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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 RCV000233537 SCV000290026 uncertain significance Charcot-Marie-Tooth disease type 2 2024-07-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 649 of the MFN2 protein (p.Arg649His). This variant is present in population databases (rs763492075, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 240945). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MFN2 protein function with a positive predictive value of 95%. 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196640 SCV001367260 uncertain significance Hereditary motor and sensory neuropathy with optic atrophy 2019-08-27 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.

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