ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.669T>A (p.Phe223Leu)

dbSNP: rs1440006845
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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 RCV003581716 SCV004291591 likely pathogenic Charcot-Marie-Tooth disease type 2 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 223 of the MFN2 protein (p.Phe223Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant Charcot-Marie-Tooth disease (PMID: 15549395, 23733358). ClinVar contains an entry for this variant (Variation ID: 637299). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Inherited Neuropathy Consortium RCV000789389 SCV000928744 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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