Submissions for variant NM_002618.4(PEX13):c.573_582del (p.Arg193fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV003335888	SCV004046128	pathogenic	PEX13-related disorder		criteria provided, single submitter	clinical testing	This frameshifting variant in exon 2 of 4 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge. Loss-of-function variation in PEX13 is an established mechanism of disease (PMID: 10332040, 20301621, 35854306). The c.573_582del (p.Arg193SerfsTer4) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.573_582del (p.Arg193SerfsTer4) variant is classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003388223	SCV004100004	pathogenic	Peroxisome biogenesis disorder	2023-09-02	criteria provided, single submitter	clinical testing	Variant summary: PEX13 c.573_582del10 (p.Arg193SerfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251416 control chromosomes (gnomAD). To our knowledge, no occurrence of c.573_582del10 in individuals affected with Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.