Submissions for variant NM_022041.3(GAN):c.1084G>A (p.Glu362Lys) (rs587779384)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000560303	SCV000640420	uncertain significance	Giant axonal neuropathy 1	2017-07-25	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid with lysine at codon 362 of the GAN protein (p.Glu362Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs587779384, ExAC 0.006%). This variant has been reported as heterozygous in an individual affected with Charcot Marie Tooth disease, type 2 (PMID: 25025039). ClinVar contains an entry for this variant (Variation ID: 157535). 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.
Dept. of Medical Genetics, Telemark Hospital Trust	RCV000144881	SCV000118592	uncertain significance	Charcot-Marie-Tooth disease	2013-11-01	no assertion criteria provided	research