ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.919A>G (p.Lys307Glu)

dbSNP: rs1639171700
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen RCV001201342 SCV001372229 uncertain significance Charcot-Marie-Tooth disease type 2A2 2020-05-19 criteria provided, single submitter clinical testing
Invitae RCV001876288 SCV002262393 likely pathogenic Charcot-Marie-Tooth disease type 2 2022-11-29 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 307 of the MFN2 protein (p.Lys307Glu). This variant is not present in population databases (gnomAD no frequency). 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. 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: 933228). This missense change has been observed in individuals with autosomal dominant Charcot-Marie-Tooth disease (PMID: 26801520; Invitae).

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