Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673928 | SCV000799185 | likely pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2018-04-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001214601 | SCV001386288 | pathogenic | Zellweger spectrum disorders | 2019-06-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala921Leufs*40) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Zellweger syndrome spectrum disorder (PMID: 21031596). ClinVar contains an entry for this variant (Variation ID: 557750). Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001293548 | SCV001482146 | pathogenic | Peroxisome biogenesis disorder | 2021-02-12 | criteria provided, single submitter | clinical testing | Variant summary: PEX1 c.2760delA (p.Ala921LeufsX40) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251160 control chromosomes (gnomAD and publication data). c.2760delA has been reported in the literature in one homozygous individual affected with Zellweger Syndrome. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic and likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Natera, |
RCV001214601 | SCV002076845 | pathogenic | Zellweger spectrum disorders | 2020-10-27 | no assertion criteria provided | clinical testing |