Submissions for variant NM_020956.2(PRX):c.*1779T>C (rs149715830)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000228501	SCV000291762	uncertain significance	Charcot-Marie-Tooth disease type 4	2020-01-06	criteria provided, single submitter	clinical testing	This sequence change replaces valine with alanine at codon 525 of the PRX protein (p.Val525Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs149715830, ExAC 0.2%). This variant has been reported in 3 individuals affected with peripheral neuropathy (PMID: 24627108, 26392352). ClinVar contains an entry for this variant (Variation ID: 242179). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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 and their clinical significance is uncertain. In summary, this variant has uncertain impact on PRX function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina	RCV001094584	SCV000413235	uncertain significance	Charcot-Marie-Tooth disease, demyelinating, type 4F	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000431721	SCV000514286	likely benign	not specified	2017-09-11	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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000658836	SCV000703932	uncertain significance	not provided	2018-05-01	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000658836	SCV000780632	uncertain significance	not provided	2019-10-01	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre	RCV000789549	SCV001335853	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Inherited Neuropathy Consortium	RCV000789549	SCV000928905	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only