Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000412294 | SCV000487623 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2016-05-27 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000410262 | SCV000487624 | pathogenic | Peroxisome biogenesis disorder 1B | 2016-05-27 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV001174676 | SCV001337909 | pathogenic | Peroxisome biogenesis disorders, Zellweger syndrome spectrum | 2020-01-10 | criteria provided, single submitter | clinical testing | Variant summary: PEX1 c.2T>C (p.Met1?) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 199938 control chromosomes (gnomAD). c.2T>C has been reported in the literature in multiple homozygous individuals affected with Zellweger Syndrome (ie. Ebberink_2010, Ghosh_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001232745 | SCV001405313 | pathogenic | Zellweger syndrome | 2020-10-26 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the PEX1 mRNA. The next in-frame methionine is located at codon 209. This variant is present in population databases (rs766020928, ExAC 0.01%). This variant has been observed in individual(s) with Zellweger spectrum disorder (PMID: 21031596,28468868). ClinVar contains an entry for this variant (Variation ID: 371746). For these reasons, this variant has been classified as Pathogenic. |
Centogene AG - |
RCV001250203 | SCV001424472 | pathogenic | Peroxisome biogenesis disorder type 1A | criteria provided, single submitter | clinical testing |