Submissions for variant NM_020956.2(PRX):c.*2459G>A (rs147587689)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001080434	SCV000255225	likely benign	Charcot-Marie-Tooth disease type 4	2019-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000236667	SCV000292668	likely benign	not specified	2017-11-10	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	RCV000416164	SCV000333623	uncertain significance	not provided	2015-08-13	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000416164	SCV000493486	likely benign	not provided	2020-01-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000236667	SCV000614799	likely benign	not specified	2016-09-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001283041	SCV001157479	uncertain significance	none provided	2020-08-26	criteria provided, single submitter	clinical testing	The PRX c.2254G>A; p.Glu752Lys variant (rs147587689), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 216834). This variant is found in the general population with an allele frequency of 0.14 % (383 /282,174 alleles, including 1 homozygotes) in the Genome Aggregation Database. The glutamic acid at codon 752 is moderately conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Glu752Lys variant is uncertain at this time. Pathogenic variants in PRX are associated with autosomal recessive Charcot-Marie-Tooth disease, type 4F (MIM: 614895) and Dejerine-Sottas disease (MIM: 145900). As no other significant variants were detected in the PRX gene, even if the p.Glu752Lys variant is later determined to be pathogenic, it alone is likely not causative for this patient’s symptoms. However, deep intronic variants, variants in the enhancer region, and large deletions and duplications are not analyzed by this method; therefore, additional variants in these regions cannot be ruled out.
Illumina Clinical Services Laboratory,Illumina	RCV001129129	SCV001288627	uncertain significance	Charcot-Marie-Tooth disease, demyelinating, type 4F	2018-01-12	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.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001172781	SCV001335849	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing