Submissions for variant NM_014874.3(MFN2):c.1071G>C (p.Lys357Asn) (rs119103261)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000547064	SCV000657708	likely pathogenic	Charcot-Marie-Tooth disease, type 2	2017-08-09	criteria provided, single submitter	clinical testing	This sequence change replaces lysine with asparagine at codon 357 of the MFN2 protein (p.Lys357Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Charcot-Marie-Tooth disease type 2 (CMT2) (PMID: 15549395). ClinVar contains an entry for this variant (Variation ID: 2274). 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. 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.
OMIM	RCV000002362	SCV000022520	pathogenic	Charcot-Marie-Tooth disease, type 2A2A	2005-01-01	no assertion criteria provided	literature only

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