ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.653T>C (p.Leu218Pro) (rs879253925)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236657 SCV000292831 uncertain significance not provided 2016-02-25 criteria provided, single submitter clinical testing The L218P variant has been previously reported as probably disease causing; however, information about the patient's phenotype and segregation analysis was not provided (Østern et al., 2013). Missense variants in nearby residues (I213T, D214N, F216S, F223L) have been reported in the Human Gene Mutation Database in association with axonal neuropathy or CMT2A (Stenson et al., 2014), supporting the functional importance of this region of the protein. L218P was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L218P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant.
Inherited Neuropathy Consortium RCV000789064 SCV000928413 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Molecular Diagnostics Laboratory,M Health: University of Minnesota RCV000761252 SCV000891209 likely pathogenic Charcot-Marie-Tooth disease, type 2A2A 2018-06-04 criteria provided, single submitter clinical testing

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