Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV003131168 | SCV003811332 | likely pathogenic | Peroxisome biogenesis disorder 12A (Zellweger) | 2022-11-10 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV004017971 | SCV004847406 | likely pathogenic | Zellweger spectrum disorders | 2023-12-28 | criteria provided, single submitter | clinical testing | The p.Leu94X variant in PEX19 has not been previously reported in individuals with Zellweger spectrum disorder disorder but has been reported in ClinVar (Variation ID 2432567). It was absent from large population studies (gnomAD, v.3.1.2). This nonsense variant leads to a premature termination codon at position 94, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the PEX19 gene is an established disease mechanism in autosomal recessive Zellweger spectrum disorder. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Zellweger spectrum disorder. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |