Submissions for variant NM_020956.2(PRX):c.*4152C>T (rs142762689)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000767048	SCV000293538	uncertain significance	not provided	2017-03-02	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the PRX gene. The A1316V variant has been reported previously in a patient with chemotherapy-induced peripheral neuropathy (CIPN); however, a second PRX variant was not identified in this individual (Beutler et al., 2014). The authors suggested that variants in the PRX gene may contribute to susceptibility to CIPN (Beutler et al., 2014). The A1316V variant is observed in 31/5286 (0.6%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1316V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina	RCV001094578	SCV000413201	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Athena Diagnostics Inc	RCV000236760	SCV000614813	likely benign	not specified	2017-06-30	criteria provided, single submitter	clinical testing
Invitae	RCV000559953	SCV000658021	likely benign	Charcot-Marie-Tooth disease type 4	2019-12-31	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000236760	SCV000859022	likely benign	not specified	2018-01-02	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173096	SCV001336172	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing