Submissions for variant NM_020956.2(PRX):c.*1596G>A (rs553211374)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000459879	SCV000551420	uncertain significance	Charcot-Marie-Tooth disease type 4	2018-12-12	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 464 of the PRX protein (p.Arg464Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs553211374, ExAC 0.009%) but has not been reported in the literature in individuals with a PRX-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.