ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.2120G>C (p.Arg707Pro) (rs375937289)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001247103 SCV001420506 likely pathogenic Charcot-Marie-Tooth disease, type 2 2019-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 707 of the MFN2 protein (p.Arg707Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 22492563, 22926664). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 637750). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg707 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18458227, 20008656, 22492563, 24126688, 25025039, 26085578). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Inherited Neuropathy Consortium RCV000790047 SCV000929437 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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