ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.1252C>T (p.Arg418Ter) (rs1057517987)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413487 SCV000491289 likely pathogenic not provided 2016-12-01 criteria provided, single submitter clinical testing The R418X variant in the MFN2 gene has been reported previously as a de novo variant in one individual with Charcot Marie Tooth type 2 with additional findings of optic atrophy and increased T2 signal on MRI in the cerebellar peduncles (Zuchner et al., 2006). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R418X variant 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 R418X variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV001219307 SCV001391240 pathogenic Charcot-Marie-Tooth disease, type 2 2019-04-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg418*) in the MFN2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Charcot-Marie-Tooth disease plus optic atrophy (PMID: 16437557). ClinVar contains an entry for this variant (Variation ID: 372790). 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.
Inherited Neuropathy Consortium RCV000789392 SCV000928747 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Institute of Human Genetics, Klinikum rechts der Isar RCV000995579 SCV001149835 likely pathogenic Hereditary motor and sensory neuropathy with optic atrophy 2019-06-07 no assertion criteria provided clinical testing

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