Total submissions: 37
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000078918 | SCV000329457 | pathogenic | not provided | 2022-06-09 | criteria provided, single submitter | clinical testing | Complementation studies found that this variant results in no functional complementation while control PEX1 cDNA rescued the impaired peroxisome biogenesis in patient cells (Ratbi et al., 2015); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28468868, 30266093, 29419819, 10447258, 20952722, 26387595, 12402331, 26643206, 26287655, 29377746, 29431110, 29261186, 30487145, 31150129, 31831025, 31054281, 30577886, 32627857, 32866347, 31980526, 31216405, 31589614, 31884617, 20301621) |
Eurofins Ntd Llc |
RCV000078918 | SCV000331295 | pathogenic | not provided | 2016-03-30 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000500705 | SCV000596391 | pathogenic | Peroxisome biogenesis disorder | 2016-04-08 | criteria provided, single submitter | clinical testing | |
Center for Pediatric Genomic Medicine, |
RCV000078918 | SCV000609514 | pathogenic | not provided | 2017-05-12 | criteria provided, single submitter | clinical testing | |
Institute Of Human Genetics Munich, |
RCV000007953 | SCV000680330 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2021-07-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000500705 | SCV000696794 | pathogenic | Peroxisome biogenesis disorder | 2017-05-15 | criteria provided, single submitter | clinical testing | Variant summary: The PEX1 c.2097dupT (p.Ile700Tyrfs) variant results in a premature termination codon, predicted to cause a truncated or absent PEX1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 77/120218 control chromosomes at a frequency of 0.0006405, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX1 variant (0.003873). The variant of interest is a common mutation that has been reported in multiple ZS affected homozygous and compound heterozygous individuals. Functional studies show that the variant results in the loss of protein function (Collins_1998). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Invitae | RCV001376645 | SCV000754536 | pathogenic | Zellweger spectrum disorders | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile700Tyrfs*42) 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 (rs61750415, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individuals with peroxisomal biogenesis disorder (PMID: 10447258, 12402331, 26287655, 26387595, 26643206, 28468868). ClinVar contains an entry for this variant (Variation ID: 7519). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000850579 | SCV000992801 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger); Heimler syndrome 1; Peroxisome biogenesis disorder 1B | 2017-12-31 | criteria provided, single submitter | clinical testing | |
Rady Children's Institute for Genomic Medicine, |
RCV000853332 | SCV000996191 | pathogenic | Peroxisome biogenesis disorder 1B | 2018-08-28 | criteria provided, single submitter | clinical testing | This frameshifting variant in exon 13 of 24 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a homozygous or compound heterozygous change in multiple patients with Zellweger spectrum disorders (PMID: 10447258). This variant is commonly observed in affected individuals with an estimated allele frequency of 0.35 among PEX1-deficient patients (PMID: 17055079). Functional studies confirm this variant results in decreased mRNA levels and loss of protein function (PMID: 10447258). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.05 % (139/276872) and thus is presumed to be rare. Based on the available evidence, the c.2097dupT (p.Ile700TyrfsTer42) variant is classified as pathogenic. |
Baylor Genetics | RCV001004324 | SCV001163205 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger); Peroxisome biogenesis disorder 1B | criteria provided, single submitter | clinical testing | ||
Myriad Genetics, |
RCV000007953 | SCV001194190 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2019-12-04 | criteria provided, single submitter | clinical testing | NM_000466.2(PEX1):c.2097dupT(aka I700Yfs*42) is classified as pathogenic in the context of peroxisome biogenesis disorder type 1. Sources cited for classification include the following: PMID 12402331, 15098231, 20952722, 21031596, 10447258 and 16141001. Classification of NM_000466.2(PEX1):c.2097dupT(aka I700Yfs*42) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.‚Äã |
Blueprint Genetics | RCV001073754 | SCV001239314 | pathogenic | Retinal dystrophy | 2017-10-15 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000078918 | SCV001246668 | pathogenic | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | PEX1: PM3:Very Strong, PVS1, PM2 |
Centre for Mendelian Genomics, |
RCV000853332 | SCV001368667 | pathogenic | Peroxisome biogenesis disorder 1B | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2. This variant was detected in homozygous state. |
UNC Molecular Genetics Laboratory, |
RCV000007953 | SCV001423858 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | criteria provided, single submitter | research | PEX1 c.2097dupT [p.I700fs] is a pathogenic frameshift variant predicted to result in premature truncation or absence of the PEX1 protein and resulting in PEX1 loss of function (PMID: 10447258). This is a rare variant that has been previously reported in Zellweger spectrum disorder (PMID:10447258; 10480353; 11389485; 12032265; 15542397; 16141001; 26387595). | |
Elsea Laboratory, |
RCV000850579 | SCV001424268 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger); Heimler syndrome 1; Peroxisome biogenesis disorder 1B | 2020-04-01 | criteria provided, single submitter | clinical testing | |
Laboratoire de Génétique Moléculaire, |
RCV000078918 | SCV001468912 | pathogenic | not provided | criteria provided, single submitter | clinical testing | ||
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000007953 | SCV002061574 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2021-09-20 | criteria provided, single submitter | clinical testing | PVS1, PS3, PM2 |
Mayo Clinic Laboratories, |
RCV000078918 | SCV002525765 | pathogenic | not provided | 2021-07-14 | criteria provided, single submitter | clinical testing | PVS1, PS3, PS4_moderate |
Centogene AG - |
RCV000853332 | SCV002598518 | pathogenic | Peroxisome biogenesis disorder 1B | 2022-09-07 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000078918 | SCV002817194 | pathogenic | not provided | 2021-09-03 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. This variant has been identified as homozygous or compound heterozygous in multiple individuals with clinical features associated with this gene and appears to segregate with disease in at least one family (PMID: 20952722, 31150129, 29377746, 30577886, 16141001, 15542397, 12032265, 11389485, 10480353, 28468868, 26387595, 26287655, 26643206, 10447258). The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org).This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study. |
Ambry Genetics | RCV002512885 | SCV003634204 | pathogenic | Inborn genetic diseases | 2021-04-20 | criteria provided, single submitter | clinical testing | The c.2097dupT (p.I700Yfs*42) alteration, located in exon 13 (coding exon 13) of the PEX1 gene, consists of a duplication of T at position 2097, causing a translational frameshift with a predicted alternate stop codon after 42 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the TT allele has an overall frequency of 0.05% (137/282532) total alleles studied. The highest observed frequency was 0.09% (119/128972) of European (non-Finnish) alleles. This mutation is common and has been reported in the homozygous and compound heterozygous state in numerous individuals with PEX1-related peroxisome biogenesis spectrum disorders (Collins, 1999; Steinberg, 2004; Rosewich, 2005; Ebberink, 2011). Based on the available evidence, this alteration is classified as pathogenic. |
Revvity Omics, |
RCV000078918 | SCV003824843 | pathogenic | not provided | 2023-11-16 | criteria provided, single submitter | clinical testing | |
Johns Hopkins Genomics, |
RCV000007953 | SCV003839139 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2022-11-22 | criteria provided, single submitter | clinical testing | c.2097dupT in PEX1 has been reported in multiple individuals affected with Zellweger spectrum disorder. This variant (rs61750415) has been reported in ClinVar (variation ID 7519), and is rare (<0.1%) in a large population dataset (gnomAD: 137/282532 total alleles; 0.0485%; no homozygotes). This frameshift variant results in a premature stop codon in exon 13 of 24, likely leading to nonsense-mediated decay and lack of protein production and has supporting functional evidence. We consider c.2097dupT;p.Ile700fs in PEX1 to be pathogenic. |
Rady Children's Institute for Genomic Medicine, |
RCV003335020 | SCV004046411 | pathogenic | PEX1-RELATED DISORDERS | criteria provided, single submitter | clinical testing | This frameshifting variant in exon 13 of 24 introduces a premature stop codon and is predicted to result in loss of normal protein function through protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported in the homozygous state and in combination with other PEX1 variants in multiple patients with Zellweger spectrum disorder (PMID: 10447258). It is one of the most common PEX1 mutations in PEX1-deficient patients (PMID: 17055079). Functional studies confirm this variant results in decreased mRNA levels and loss of protein function (PMID: 10447258). The c.2097dupT (p.Ile700TyrfsTer42) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.05% (137/282532) and thus is presumed to be rare. Based on the available evidence, the c.2097dupT (p.Ile700TyrfsTer42) variant is classified as Pathogenic. | |
Preventiongenetics, |
RCV003415676 | SCV004114848 | pathogenic | PEX1-related condition | 2023-08-04 | criteria provided, single submitter | clinical testing | The PEX1 c.2097dupT variant is predicted to result in a frameshift and premature protein termination (p.Ile700Tyrfs*42). This variant has been reported in both the homozygous and compound heterozygous states in multiple patients with Zellweger syndrome (Maxwell et al. 2002. PubMed ID: 12402331; Berendse et al. 2016. PubMed ID: 26287655; Rush et al. 2016. PubMed ID: 26643206; Ghosh et al. 2017. PubMed ID: 28468868). Notably, one patient with this variant in the compound heterozygous state with another pathogenic PEX1 variant showed a milder phenotype with survival into adulthood (Berendse et al. 2016. PubMed ID: 26287655). However, two functional studies have reported that this variant severely affects peroxisomal function (Maxwell et al. 2002. PubMed ID: 12402331; Ratbi et al. 2015. PubMed ID: 26387595). This variant is reported in 0.092% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org). In summary, we interpret this variant as pathogenic. |
Baylor Genetics | RCV000201307 | SCV004203260 | pathogenic | Heimler syndrome 1 | 2023-10-28 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000007953 | SCV000028158 | pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2015-10-01 | no assertion criteria provided | literature only | |
OMIM | RCV000201307 | SCV000256088 | pathogenic | Heimler syndrome 1 | 2015-10-01 | no assertion criteria provided | literature only | |
Gene |
RCV000500705 | SCV001478319 | not provided | Peroxisome biogenesis disorder | no assertion provided | literature only | NM_000466.2:c.2097dupT and NM_000466.2:c.2528G>A are the most common PEX1 variants; about 80% of persons with a PEX1 pathogenic variant have at least 1 of these common alleles. | |
Diagnostic Laboratory, |
RCV000078918 | SCV001741006 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000078918 | SCV001808480 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000078918 | SCV001922150 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000078918 | SCV001957229 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000078918 | SCV001972332 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Natera, |
RCV001376645 | SCV002076876 | pathogenic | Zellweger spectrum disorders | 2017-03-17 | no assertion criteria provided | clinical testing | |
Zotz- |
RCV000201307 | SCV004099366 | pathogenic | Heimler syndrome 1 | 2023-10-30 | no assertion criteria provided | clinical testing |