ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.404G>A (p.Arg135Gln)

gnomAD frequency: 0.00001  dbSNP: rs1443036026
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694043 SCV000822469 uncertain significance Charcot-Marie-Tooth disease type 2 2021-12-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 135 of the MFN2 protein (p.Arg135Gln). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 not expected to disrupt MFN2 protein function. ClinVar contains an entry for this variant (Variation ID: 549683). This missense change has been observed in individual(s) with autosomal recessive Charcot-Marie-Tooth disease (PMID: 29858556). This variant is present in population databases (no rsID available, gnomAD 0.01%).
Institute of Human Genetics, Cologne University RCV000664229 SCV000787794 likely pathogenic Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; 2018-04-25 no assertion criteria provided clinical testing

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