ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.406dup (p.Val136fs) (rs759844257)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521500 SCV000620139 likely pathogenic not provided 2017-08-15 criteria provided, single submitter clinical testing The c.406dupG variant in the MFN2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.406dupG variant causes a frameshift starting with codon Valine 136, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Val136GlyfsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.406dupG variant is not observed in the homozygous state or at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.406dupG as a likely pathogenic variant.
Invitae RCV001062795 SCV001227618 pathogenic Charcot-Marie-Tooth disease, type 2 2020-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val136Glyfs*8) in the MFN2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs759844257, ExAC 0.001%). This variant has not been reported in the literature in individuals with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 451440). Loss-of-function variants in MFN2 are known to be pathogenic (PMID: 16714318, 21715711, 26955893). For these reasons, this variant has been classified as Pathogenic.

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