ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.1144G>C (p.Ala382Pro) (rs1553144066)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000653868 SCV000775758 likely pathogenic Charcot-Marie-Tooth disease, type 2 2019-11-22 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 382 of the MFN2 protein (p.Ala382Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine 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: 23456260). It has also been observed to segregate with disease in related individuals. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ala382 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been observed in individuals with MFN2-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. 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 RCV000789364 SCV000928719 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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