Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671411 | SCV000796385 | uncertain significance | Peroxisome biogenesis disorder 1A (Zellweger) | 2017-12-12 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001322950 | SCV001513846 | uncertain significance | Zellweger spectrum disorders | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1275*) in the PEX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the PEX1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 555569). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001779049 | SCV002014900 | uncertain significance | not specified | 2021-10-14 | criteria provided, single submitter | clinical testing | Variant summary: PEX1 c.3823C>T (p.Arg1275X) results in a premature termination codon in exon 24 (i.e. in the last exon) of the gene that is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein. The variant is predicted to remove 9 amino-acids from the C-terminal end of the protein, in the gene PEX1 for which loss-of-function is a known mechanism of disease. The variant allele was found at a frequency of 1.2e-05 in 248532 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3823C>T in individuals affected with Zellweger Syndrome (ZS) and no experimental evidence demonstrating its impact on protein function have been reported. A truncating variant (i.e. c.3750G>A (p.Trp1250*)) upstream from this position have been reported in homozygous individuals affected with an attenuated phenotype representing the milder end of the ZS spectrum (PMID 26387595), and functional studies confirmed the hypomorphic effect of this variant (PMID 26387595). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, although the variant is unlikely to cause a severe ZS phenotype, a potential hypomorphic effect resulting from a partially functional protein cannot be excluded, therefore the variant was classified as uncertain significance. |
| Natera, |
RCV001322950 | SCV002076051 | uncertain significance | Zellweger spectrum disorders | 2017-09-17 | no assertion criteria provided | clinical testing |