Submissions for variant NM_020956.2(PRX):c.*3980G>A (rs751742049)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000438962	SCV000529930	likely benign	not specified	2016-07-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000546648	SCV000658017	uncertain significance	Charcot-Marie-Tooth disease type 4	2017-04-22	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid with lysine at codon 1259 of the PRX protein (p.Glu1259Lys). 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 (rs751742049, ExAC 0.2%) but has not been reported in the literature in individuals with a PRX-related disease. ClinVar contains an entry for this variant (Variation ID: 387796). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina	RCV001135977	SCV001295789	uncertain significance	Charcot-Marie-Tooth disease, demyelinating, type 4F	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.