ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.718T>G (p.Phe240Val)

dbSNP: rs1557525005
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000687000 SCV000814547 pathogenic Charcot-Marie-Tooth disease type 2 2018-08-17 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to segregate with Charcot-Marie-Tooth disease in several families (PMID: 26382835, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with valine at codon 240 of the MFN2 protein (p.Phe240Val). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and valine. A different missense substitution at this codon (p.Phe240Leu) has been determined to be pathogenic (Invitae). This suggests that the phenylalanine residue is critical for MFN2 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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