ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2097dup (p.Ile700fs) (rs61750415)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000850579 SCV000992801 pathogenic Peroxisome biogenesis disorder 1A (Zellweger); Deafness enamel hypoplasia nail defects; Peroxisome biogenesis disorder 1B 2017-12-31 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000078918 SCV000609514 pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing
Counsyl RCV000007953 SCV000678015 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2015-07-29 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078918 SCV000331295 pathogenic not provided 2016-03-30 criteria provided, single submitter clinical testing
GeneDx RCV000078918 SCV000329457 pathogenic not provided 2018-11-08 criteria provided, single submitter clinical testing The c.2097dupT variant in the PEX1 gene has been reported previously, sometimes as c.2098insT (Steinberg et al., 2017). This variant is one of the most common pathogenic variants in the PEX1 gene, and in the homozygous state it is usually associated with a severe phenotype (Steinberg et al., 2017). The c.2097dupT variant causes a frameshift starting with codon Isoleucine 700, changes this amino acid to a Tyrosine residue, and creates a premature Stop codon at position 42 of the new reading frame, denoted p.Ile700TyrfsX42. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret c.2097dupT as a pathogenic variant.
Genetic Services Laboratory, University of Chicago RCV000500705 SCV000596391 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2016-04-08 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000007953 SCV000680330 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2017-11-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000500705 SCV000696794 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 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 RCV000007953 SCV000754536 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2019-01-03 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. This variant is present in population databases (rs61750415, ExAC 0.1%). This variant has been reported as homozygous or in combination with another PEX1 variant in many individuals affected with a peroxisomal biogenesis disorder (PMID:  10447258, 26643206, 26287655, 12402331, 26387595, 28468868). ClinVar contains an entry for this variant (Variation ID: 7519). 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.
OMIM RCV000007953 SCV000028158 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2015-10-01 no assertion criteria provided literature only
OMIM RCV000201307 SCV000256088 pathogenic Deafness enamel hypoplasia nail defects 2015-10-01 no assertion criteria provided literature only

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