ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.1082A>G (p.His361Arg) (rs1064793170)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485629 SCV000565131 likely pathogenic not provided 2015-02-19 criteria provided, single submitter clinical testing A novel H361R variant that is likely pathogenic was identified in the MFN2 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The H361R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, this substitution occurs at a position that is highly conserved across species and the H361R variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. Furthermore, missense variants in the same residue (H361Y) and in nearby residues (T356A, K357N, T362M, R364W/Q/O, M376L) have been reported in the Human Gene Mutation Database in association with Charcot-Marie-Tooth disease (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000485629 SCV001247288 pathogenic not provided 2019-03-01 criteria provided, single submitter clinical testing

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