Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169227 | SCV000220493 | likely pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2014-07-10 | criteria provided, single submitter | literature only | |
Eurofins Ntd Llc |
RCV000657614 | SCV000226030 | pathogenic | not provided | 2014-10-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000657614 | SCV000779356 | likely pathogenic | not provided | 2018-05-16 | criteria provided, single submitter | clinical testing | The R795X variant in the PEX1 gene has been reported previously, along with a second variant in PEX1, in an individual with Zellweger syndrome (Collins and Gould, 1999). R795X has also been reported in the heterozygous state in an additional unrelated individual with a Zellweger spectrum disorder, however, there was no mention of a second variant being identified (Ebberink et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R795X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R795X as a likely pathogenic variant. |
Baylor Genetics | RCV001004323 | SCV001163204 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger); Peroxisome biogenesis disorder 1B | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001220088 | SCV001392061 | pathogenic | Zellweger spectrum disorders | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg795*) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 21031596, 26387595, 31831025). This variant is present in population databases (rs61750418, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with Zellweger syndrome (PMID: 10447258, 21846392). ClinVar contains an entry for this variant (Variation ID: 188873). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265653 | SCV002548036 | pathogenic | Peroxisome biogenesis disorder | 2022-05-05 | criteria provided, single submitter | clinical testing | Variant summary: PEX1 c.2383C>T (p.Arg795X) 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 allele was found at a frequency of 1.6e-05 in 251216 control chromosomes (gnomAD). c.2383C>T has been reported in the literature in individuals affected with Zellweger Syndrome (Collins_1999, Rosewich_2005, Ebberink_2011, Thoms_2011, Wang_2021). These data indicate that the variant is likely to 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/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV003474901 | SCV004203266 | pathogenic | Heimler syndrome 1 | 2023-10-18 | criteria provided, single submitter | clinical testing |