Submissions for variant NM_014874.4(MFN2):c.1612C>G (p.Gln538Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV004527826	SCV004111862	uncertain significance	MFN2-related disorder	2023-02-10	criteria provided, single submitter	clinical testing	The MFN2 c.1612C>G variant is predicted to result in the amino acid substitution p.Gln538Glu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003745594	SCV004537672	uncertain significance	Charcot-Marie-Tooth disease type 2	2023-09-24	criteria provided, single submitter	clinical testing	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. This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 538 of the MFN2 protein (p.Gln538Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. 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.