ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.1118G>A (p.Arg373Gln)

gnomAD frequency: 0.00001  dbSNP: rs142042485
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000535795 SCV000657710 uncertain significance Charcot-Marie-Tooth disease type 2 2024-10-02 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 373 of the MFN2 protein (p.Arg373Gln). This variant is present in population databases (rs142042485, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 476765). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MFN2 protein function. 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.
Molecular Genetics Laboratory, London Health Sciences Centre RCV001172685 SCV001335751 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Ambry Genetics RCV002438491 SCV002752712 uncertain significance Inborn genetic diseases 2019-09-27 criteria provided, single submitter clinical testing The p.R373Q variant (also known as c.1118G>A), located in coding exon 9 of the MFN2 gene, results from a G to A substitution at nucleotide position 1118. The arginine at codon 373 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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