ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.820C>T (p.Arg274Trp)

gnomAD frequency: 0.00002  dbSNP: rs762440627
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001970191 SCV002235169 pathogenic Charcot-Marie-Tooth disease type 2 2023-06-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 274 of the MFN2 protein (p.Arg274Trp). This variant is present in population databases (rs762440627, gnomAD 0.006%). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1456072). This missense change has been observed in individual(s) with autosomal dominant hereditary motor and sensory neuropathy with additional mild intellectual disability (PMID: 26581383). In at least one individual the variant was observed to be de novo.

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