Submissions for variant NM_001136473.1(LITAF):c.268C>T (p.Arg90Cys) (rs375665454)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000794470	SCV000933881	uncertain significance	Charcot-Marie-Tooth disease, type 1C	2019-03-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with cysteine at codon 90 of the LITAF protein (p.Arg90Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs375665454, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with LITAF-related disease. 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 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 Centre	RCV001173625	SCV001336726	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing

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