Submissions for variant NM_181882.3(PRX):c.3098del (p.Thr1033fs)

dbSNP: rs2145727241

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3billion	RCV002250961	SCV002521222	likely pathogenic	Charcot-Marie-Tooth disease type 4F	2022-05-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10%. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003094076	SCV002968450	pathogenic	Charcot-Marie-Tooth disease type 4	2022-01-23	criteria provided, single submitter	clinical testing	This variant disrupts a region of the PRX protein in which other variant(s) (p.Arg1070*) have been determined to be pathogenic (PMID: 15197604, 16770524, 22847150, 26059842). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Thr1033Metfs*6) in the PRX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 429 amino acid(s) of the PRX protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PRX-related conditions. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV002250961	SCV004807489	pathogenic	Charcot-Marie-Tooth disease type 4F	2024-03-29	criteria provided, single submitter	clinical testing