Submissions for variant NM_006158.4(NEFL):c.637A>G (p.Ile213Val) (rs538481538)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000800798	SCV000940533	uncertain significance	Charcot-Marie-Tooth disease type 2E	2019-02-20	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine with valine at codon 213 of the NEFL protein (p.Ile213Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual and a family affected with Charcot-Marie-Tooth disease (Invitae). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Genetics Laboratory, London Health Sciences Center	RCV001172739	SCV001335805	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing