ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.1367C>T (p.Pro456Leu)

gnomAD frequency: 0.00001  dbSNP: rs78658090
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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 RCV001906969 SCV002181068 uncertain significance Charcot-Marie-Tooth disease type 2 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 456 of the MFN2 protein (p.Pro456Leu). 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. 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: 1406678). This missense change has been observed in individual(s) with early-onset stroke (PMID: 18490623). This variant is present in population databases (rs78658090, gnomAD 0.006%).

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