ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.2171T>C (p.Leu724Pro) (rs1557537346)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695484 SCV000823987 likely pathogenic Charcot-Marie-Tooth disease, type 2 2018-05-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 724 of the MFN2 protein (p.Leu724Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease (CMT) (PMID: 21326314, 24450158, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000789361 SCV000928716 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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