VCV000007519.92 - ClinVar

NM_000466.3(PEX1):c.2097dup (p.Ile700fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(38)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000466.3(PEX1):c.2097dup (p.Ile700fs)

Variation ID: 7519 Accession: VCV000007519.92

Type and length

Duplication, 1 bp

Location

Cytogenetic: 7q21.2 7: 92503169-92503170 (GRCh38) [ NCBI UCSC ] 7: 92132483-92132484 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Oct 20, 2024	Mar 30, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000466.3:c.2097dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000457.1:p.Ile700fs	frameshift
NM_000466.3:c.2097dupT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001282677.2:c.1926dup	NP_001269606.1:p.Ile643fs	frameshift
NM_001282678.2:c.1473dup	NP_001269607.1:p.Ile492fs	frameshift
NC_000007.14:g.92503172dup
NC_000007.13:g.92132486dup
NG_008341.2:g.30362dup

... more HGVS ... less HGVS

Protein change

I643fs, I492fs, I700fs

Other names

p.Ile700Tyrfs*42

Canonical SPDI

NC_000007.14:92503169:AAA:AAAA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA213121 OMIM: 602136.0004 OMIM: 602136.0010 dbSNP: rs61750415 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 10447258 Fig. 1 to determine the location of this allele on the current reference sequence.

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PEX1		-	-	GRCh38 GRCh37	1288	1869

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Peroxisome biogenesis disorder 1A (Zellweger)	Pathogenic (7)	criteria provided, multiple submitters, no conflicts	Nov 22, 2022	RCV000007953.34
not provided	Pathogenic (13)	criteria provided, multiple submitters, no conflicts	Nov 16, 2023	RCV000078918.58
Heimler syndrome 1	Pathogenic (3)	criteria provided, single submitter	Mar 30, 2024	RCV000201307.12
Peroxisome biogenesis disorder	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	May 15, 2017	RCV000500705.15
Heimler syndrome 1 Peroxisome biogenesis disorder 1A (Zellweger) Peroxisome biogenesis disorder 1B	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Apr 1, 2020	RCV000850579.11
Peroxisome biogenesis disorder 1B	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Sep 7, 2022	RCV000853332.12
Peroxisome biogenesis disorder 1A (Zellweger) Peroxisome biogenesis disorder 1B	Pathogenic (1)	criteria provided, single submitter	-	RCV001004324.9
Retinal dystrophy	Pathogenic (1)	criteria provided, single submitter	Oct 15, 2017	RCV001073754.10
Zellweger spectrum disorders	Pathogenic (2)	criteria provided, single submitter	Jan 31, 2024	RCV001376645.15
PEX1-related disorder	Pathogenic (2)	criteria provided, single submitter	-	RCV003415676.7
Inborn genetic diseases	Pathogenic (1)	criteria provided, single submitter	Apr 20, 2021	RCV002512885.9
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Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 15, 2017)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Peroxisome biogenesis disorder Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000696794.1 First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017	Publications: PubMed (1) PubMed: 10447258 Comment: 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 … (more) 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. (less)
Pathogenic (Dec 04, 2019)	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019)) Method: clinical testing	Peroxisome biogenesis disorder 1A (Zellweger) Affected status: unknown Allele origin: unknown	Myriad Genetics, Inc. Accession: SCV001194190.2 First in ClinVar: Apr 06, 2020 Last updated: Jul 04, 2020	Publications: PubMed (6) PubMed: 12402331‚ 15098231‚ 20952722‚ 21031596‚ 10447258‚ 16141001 Comment: NM_000466.2(PEX1):c.2097dupT(aka I700Yfs42) is classified as pathogenic in the context of peroxisome biogenesis disorder type 1. Sources cited for classification include the following: PMID 12402331, 15098231, … (more) NM_000466.2(PEX1):c.2097dupT(aka I700Yfs42) 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.â€šÃ„Ã¶âˆšÃ‘âˆšÂ£ (less)
Pathogenic (Apr 01, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Heimler syndrome 1 Peroxisome biogenesis disorder 1A (Zellweger) Peroxisome biogenesis disorder 1B Affected status: no Allele origin: maternal	Elsea Laboratory, Baylor College of Medicine Accession: SCV001424268.1 First in ClinVar: Jul 26, 2020 Last updated: Jul 26, 2020	Sex: female Testing laboratory: Org: 1006
Pathogenic (Jan 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peroxisome biogenesis disorder 1B Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001368667.2 First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020	Comment: 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.
Pathogenic (Sep 20, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peroxisome biogenesis disorder 1A (Zellweger) Affected status: yes Allele origin: germline	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center Accession: SCV002061574.3 First in ClinVar: Jan 22, 2022 Last updated: Aug 05, 2023	Comment: PVS1, PS3, PM2
Pathogenic (Sep 03, 2021)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV002817194.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Comment: 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 … (more) 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. (less)
Pathogenic (Apr 20, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV003634204.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Publications: PubMed (4) PubMed: 10447258‚ 15542397‚ 16141001‚ 21031596 Comment: The c.2097dupT (p.I700Yfs42) alteration, located in exon 13 (coding exon 13) of the PEX1 gene, consists of a duplication of T at position 2097, causing … (more) The c.2097dupT (p.I700Yfs42) 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. (less)
Pathogenic (Mar 30, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Heimler syndrome 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004203260.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Pathogenic (Apr 08, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peroxisome biogenesis disorder Affected status: yes Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000596391.1 First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017
Pathogenic (May 12, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000609514.1 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Pathogenic (Mar 30, 2016)	criteria provided, single submitter (EGL Classification Definitions) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000331295.3 First in ClinVar: Dec 06, 2016 Last updated: Jul 30, 2019	Publications: PubMed (1) PubMed: 23757202 Other databases http://geneticslab.emory.edu/emv… http://geneticslab.emory.edu/emvclass/emvclass.php?approved_symbol=PEX1 Number of individuals with the variant: 4 Zygosity: Single Heterozygote Sex: mixed
Pathogenic (Dec 31, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Heimler syndrome 1 Peroxisome biogenesis disorder 1A (Zellweger) Peroxisome biogenesis disorder 1B Affected status: yes Allele origin: germline	Baylor Genetics Accession: SCV000992801.1 First in ClinVar: Sep 21, 2019 Last updated: Sep 21, 2019	Publications: PubMed (7) PubMed: 10447258‚ 26287655‚ 28468868‚ 12402331‚ 26387595‚ 26643206‚ 20952722
Pathogenic (Aug 28, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	PEROXISOME BIOGENESIS DISORDER 1B Affected status: yes Allele origin: germline	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego Accession: SCV000996191.1 First in ClinVar: Oct 20, 2019 Last updated: Oct 20, 2019	Comment: 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. … (more) 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. (less) Number of individuals with the variant: 1
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peroxisome biogenesis disorder 1A (Zellweger) Peroxisome biogenesis disorder 1B Affected status: unknown Allele origin: germline	Baylor Genetics Accession: SCV001163205.1 First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020
Pathogenic (Oct 15, 2017)	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme) Method: clinical testing	Retinal dystrophy Affected status: yes Allele origin: germline	Blueprint Genetics Accession: SCV001239314.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 Comment: My Retina Tracker patient
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Peroxisome biogenesis disorder 1A (Zellweger) Affected status: unknown Allele origin: germline	UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill Study: CSER_NCGENES_2 Accession: SCV001423858.1 First in ClinVar: Jul 26, 2020 Last updated: Jul 26, 2020	Publications: PubMed (7) PubMed: 10447258‚ 10480353‚ 11389485‚ 12032265‚ 15542397‚ 16141001‚ 26387595 Comment: 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 … (more) 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). (less) Number of individuals with the variant: 1
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: yes Allele origin: germline	Laboratoire de Génétique Moléculaire, CHU Bordeaux Accession: SCV001468912.1 First in ClinVar: Jan 17, 2021 Last updated: Jan 17, 2021
Pathogenic (Jul 14, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV002525765.1 First in ClinVar: Jun 11, 2022 Last updated: Jun 11, 2022	Publications: PubMed (4) PubMed: 10447258‚ 26287655‚ 28468868‚ 12402331 Comment: PVS1, PS3, PS4_moderate
Pathogenic (Sep 07, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peroxisome biogenesis disorder 1B Affected status: yes Allele origin: germline	Centogene AG - the Rare Disease Company Accession: SCV002598518.1 First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022
Pathogenic (Jul 27, 2021)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Peroxisome biogenesis disorder 1A (Zellweger) (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited, germline	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV000680330.2 First in ClinVar: Jan 06, 2018 Last updated: Dec 24, 2022	Observation 1: Number of individuals with the variant: 1 Clinical Features: Abnormal facial shape (present) Observation 2: Number of individuals with the variant: 1 Clinical Features: Atrial septal defect (present) , Corneal opacity (present) , Pulmonary arterial hypertension (present) , Large fontanelles (present) , Neonatal respiratory distress (present)
Pathogenic (Jun 09, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000329457.9 First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023	Comment: 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 … (more) 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) (less)
Pathogenic (Nov 22, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peroxisome biogenesis disorder 1A (Zellweger) Affected status: unknown Allele origin: germline	Johns Hopkins Genomics, Johns Hopkins University Accession: SCV003839139.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023	Publications: PubMed (4) PubMed: 10447258‚ 11389485‚ 15542397‚ 26387595 Comment: 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), … (more) 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. (less)
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	PEX1-RELATED DISORDERS Affected status: yes Allele origin: germline	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego Accession: SCV004046411.1 First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023	Comment: 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 … (more) 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. (less)
Pathogenic (Nov 16, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003824843.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Pathogenic (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Zellweger spectrum disorders Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000754536.8 First in ClinVar: Jan 06, 2018 Last updated: Feb 20, 2024	Publications: PubMed (9) PubMed: 28492532‚ 21031596‚ 26387595‚ 31831025‚ 10447258‚ 12402331‚ 26287655‚ 26643206‚ 28468868 Comment: This sequence change creates a premature translational stop signal (p.Ile700Tyrfs42) in the PEX1 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Ile700Tyrfs42) 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. (less)
Pathogenic (Nov 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001246668.26 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Comment: PEX1: PM3:Very Strong, PVS1, PM2 Number of individuals with the variant: 15
Pathogenic (Oct 01, 2015)	no assertion criteria provided Method: literature only	PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000028158.2 First in ClinVar: Apr 04, 2013 Last updated: Jun 03, 2023	Publications: PubMed (6) PubMed: 1301993‚ 9398847‚ 10447258‚ 17055079‚ 2063923‚ 26387595 Comment on evidence: In 3 patients with Zellweger syndrome (PBD1A; 214100), including a severely affected patient who was studied by Gartner et al. (1992) (patient PBD002) and another … (more) In 3 patients with Zellweger syndrome (PBD1A; 214100), including a severely affected patient who was studied by Gartner et al. (1992) (patient PBD002) and another patient in whom Reuber et al. (1997) had identified a PEX1 splice donor mutation, Collins and Gould (1999) identified homozygosity or compound heterozygosity for a 1-bp insertion (c.2097insT) in exon 13 of the PEX1 gene. Screening for 2097insT in 32 additional CG1 patients revealed that 3 were homozygous and 12 heterozygous for the insertion. The authors concluded that 2097insT is a common allele in the CG1 patient population, and noted that in contrast to the other common mutation, G843D (602136.0001), which is associated with a trend toward the mild end of the ZS phenotypic spectrum, this second common PEX1 mutation is associated with severe phenotypes. Steinberg et al. (2006) gave the allele frequency of this mutation as 0.35 in PEX1-deficient patients. In a brother and sister with Heimler syndrome-1 (HMLR1; 234580), originally reported by Heimler et al. (1991), Ratbi et al. (2015) identified compound heterozygosity for the c.2097dupT mutation (c.2097dupT, NM_000466.2) in the PEX1 gene and a c.2114T-G transversion, resulting in a leu705-to-trp (L705W; 602136.0006) substitution. In an unrelated 24-year-old woman with HMLR1, they identified compound heterozygosity for the 2097dupT mutation and a c.1742G-C transversion, resulting in an arg581-to-pro (R581P; 602136.0007) substitution. The mutations segregated with disease in both families, and were not found in 770 in-house exomes; in addition, the L705W mutation was not found in public databases, whereas the R581P mutation was present in 1 of 121,398 alleles in the ExAC Browser (minor allele frequency less than 0.000033). The 3 affected individuals all had sensorineural hearing loss, enamel hypoplasia, and nail defects, but did not exhibit dysmorphism or additional neurologic features. Complementation assays in transfected PEX1-null cells demonstrated that the c.2097dupT variant resulted in no complementation, whereas transfection with the c.1742G-C and c.2114T-G variants rescued peroxisomal biogenesis in 23% and 58% of cells, respectively. (less)
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001741006.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Pathogenic (Mar 17, 2017)	no assertion criteria provided Method: clinical testing	Zellweger syndrome Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002076876.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022
Pathogenic (Oct 30, 2023)	no assertion criteria provided Method: clinical testing	Heimler syndrome 1 Affected status: yes Allele origin: germline	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas Accession: SCV004099366.1 First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023
Pathogenic (Nov 15, 2023)	no assertion criteria provided Method: clinical testing	Peroxisome biogenesis disorder 1A (Zellweger) Affected status: yes Allele origin: germline	Diagnostics Centre, Carl Von Ossietzky University Oldenburg Accession: SCV005049568.1 First in ClinVar: Jun 09, 2024 Last updated: Jun 09, 2024	Publications: PubMed (3) PubMed: 10447258‚ 15098231‚ 16141001 Comment: The variant PEX1:c.2097dupT, p.(Ile700Tyrfs42), which is located in the coding exon 13 of the PEX1 gene, results from a single-base insertion at nucleotide position c.2097. … (more) The variant PEX1:c.2097dupT, p.(Ile700Tyrfs42), which is located in the coding exon 13 of the PEX1 gene, results from a single-base insertion at nucleotide position c.2097. The variant causes a frameshift that results in the replace of an isoleucine by a tyrosine at protein position 700, followed by a premature translation stop codon after 42 amino acids. The variant affects an exon (13/24) present in a biologically relevant transcript and is predicted to cause protein truncation/absent due to nonsense mediated decay in a gene where loss-of-function is a known mechanism of disease. The variant has been consistently described as Pathogenic or Likely pathogenic in 37 entries in ClinVar (ClinVar ID: 7519). The variant has been described in multiple publications in homozygous and compound heterozygous state in patients with peroxisomal diseases and represents one of the most frequent pathogenic changes in Zellweger syndrome (PMID: 10447258, 15098231, 16141001). The variant is classified as rare in the overall population (allele frequency= 0.0007808 in gnomAD, v4.1.0). In summary, this variant is classified as Pathogenic. (less) Number of individuals with the variant: 1 Age: 0-9 years Sex: female
Pathogenic (Aug 16, 2024)	no assertion criteria provided Method: clinical testing	PEX1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004114848.3 First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024	Comment: The PEX1 c.2097dupT variant is predicted to result in a frameshift and premature protein termination (p.Ile700Tyrfs42). This variant has been reported in both the homozygous … (more) The PEX1 c.2097dupT variant is predicted to result in a frameshift and premature protein termination (p.Ile700Tyrfs42). 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. In summary, we interpret this variant as pathogenic. (less)
Pathogenic (Oct 01, 2015)	no assertion criteria provided Method: literature only	HEIMLER SYNDROME 1 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000256088.1 First in ClinVar: Oct 31, 2015 Last updated: Oct 31, 2015	Publications: PubMed (6) PubMed: 1301993‚ 9398847‚ 10447258‚ 17055079‚ 2063923‚ 26387595 Comment on evidence: In 3 patients with Zellweger syndrome (PBD1A; 214100), including a severely affected patient who was studied by Gartner et al. (1992) (patient PBD002) and another … (more) In 3 patients with Zellweger syndrome (PBD1A; 214100), including a severely affected patient who was studied by Gartner et al. (1992) (patient PBD002) and another patient in whom Reuber et al. (1997) had identified a PEX1 splice donor mutation, Collins and Gould (1999) identified homozygosity or compound heterozygosity for a 1-bp insertion (c.2097insT) in exon 13 of the PEX1 gene. Screening for 2097insT in 32 additional CG1 patients revealed that 3 were homozygous and 12 heterozygous for the insertion. The authors concluded that 2097insT is a common allele in the CG1 patient population, and noted that in contrast to the other common mutation, G843D (602136.0001), which is associated with a trend toward the mild end of the ZS phenotypic spectrum, this second common PEX1 mutation is associated with severe phenotypes. Steinberg et al. (2006) gave the allele frequency of this mutation as 0.35 in PEX1-deficient patients. In a brother and sister with Heimler syndrome-1 (HMLR1; 234580), originally reported by Heimler et al. (1991), Ratbi et al. (2015) identified compound heterozygosity for the c.2097dupT mutation (c.2097dupT, NM_000466.2) in the PEX1 gene and a c.2114T-G transversion, resulting in a leu705-to-trp (L705W; 602136.0006) substitution. In an unrelated 24-year-old woman with HMLR1, they identified compound heterozygosity for the 2097dupT mutation and a c.1742G-C transversion, resulting in an arg581-to-pro (R581P; 602136.0007) substitution. The mutations segregated with disease in both families, and were not found in 770 in-house exomes; in addition, the L705W mutation was not found in public databases, whereas the R581P mutation was present in 1 of 121,398 alleles in the ExAC Browser (minor allele frequency less than 0.000033). The 3 affected individuals all had sensorineural hearing loss, enamel hypoplasia, and nail defects, but did not exhibit dysmorphism or additional neurologic features. Complementation assays in transfected PEX1-null cells demonstrated that the c.2097dupT variant resulted in no complementation, whereas transfection with the c.1742G-C and c.2114T-G variants rescued peroxisomal biogenesis in 23% and 58% of cells, respectively. (less)
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001808480.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001922150.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Likely pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001957229.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001972332.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021
not provided (-)	no classification provided Method: literature only	Peroxisome biogenesis disorder Affected status: unknown Allele origin: germline	GeneReviews Accession: SCV001478319.2 First in ClinVar: Jan 30, 2021 Last updated: Oct 01, 2022	Publications: PubMed (2) PubMed: 20301621‚ 10447258 BookShelf: NBK1448 BookShelf: NBK1448 Comment: 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 … (more) 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. (less)
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Comment:

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.

Comment:

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.â€šÃ„Ã¶âˆšÃ‘âˆšÂ£

Comment:

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.

Comment:

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.

Comment:

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.

Comment:

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).

Comment:

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)

Comment:

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.

Comment:

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.

Comment:

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.

Comment:

The variant PEX1:c.2097dupT, p.(Ile700Tyrfs*42), which is located in the coding exon 13 of the PEX1 gene, results from a single-base insertion at nucleotide position c.2097. The variant causes a frameshift that results in the replace of an isoleucine by a tyrosine at protein position 700, followed by a premature translation stop codon after 42 amino acids. The variant affects an exon (13/24) present in a biologically relevant transcript and is predicted to cause protein truncation/absent due to nonsense mediated decay in a gene where loss-of-function is a known mechanism of disease. The variant has been consistently described as Pathogenic or Likely pathogenic in 37 entries in ClinVar (ClinVar ID: 7519). The variant has been described in multiple publications in homozygous and compound heterozygous state in patients with peroxisomal diseases and represents one of the most frequent pathogenic changes in Zellweger syndrome (PMID: 10447258, 15098231, 16141001). The variant is classified as rare in the overall population (allele frequency= 0.0007808 in gnomAD, v4.1.0). In summary, this variant is classified as Pathogenic.

Comment:

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. In summary, we interpret this variant as pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Expanding the clinical and genetic spectrum of Heimler syndrome.	Gao FJ	Orphanet journal of rare diseases	2019	PMID: 31831025
Diagnosing childhood-onset inborn errors of metabolism by next-generation sequencing.	Ghosh A	Archives of disease in childhood	2017	PMID: 28468868
Low bone mineral density is a common feature of Zellweger spectrum disorders.	Rush ET	Molecular genetics and metabolism	2016	PMID: 26643206
Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood.	Berendse K	Journal of inherited metabolic disease	2016	PMID: 26287655
Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6.	Ratbi I	American journal of human genetics	2015	PMID: 26387595
Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder.	Ebberink MS	Human mutation	2011	PMID: 21031596
Germinal matrix hemorrhage in Zellweger syndrome.	Takenouchi T	Journal of child neurology	2010	PMID: 20952722
Peroxisome biogenesis disorders.	Steinberg SJ	Biochimica et biophysica acta	2006	PMID: 17055079
Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations.	Rosewich H	Journal of medical genetics	2005	PMID: 16141001
The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum.	Steinberg S	Molecular genetics and metabolism	2004	PMID: 15542397
Peroxisome biogenesis disorders with prolonged survival: phenotypic expression in a cohort of 31 patients.	Poll-The BT	American journal of medical genetics. Part A	2004	PMID: 15098231
Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients.	Maxwell MA	Human mutation	2002	PMID: 12402331
PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease.	Preuss N	Pediatric research	2002	PMID: 12032265
Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels.	Walter C	American journal of human genetics	2001	PMID: 11389485
A common PEX1 frameshift mutation in patients with disorders of peroxisome biogenesis correlates with the severe Zellweger syndrome phenotype.	Maxwell MA	Human genetics	1999	PMID: 10480353
Identification of a common PEX1 mutation in Zellweger syndrome.	Collins CS	Human mutation	1999	PMID: 10447258
Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.	Reuber BE	Nature genetics	1997	PMID: 9398847
Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome.	Gärtner J	Nature genetics	1992	PMID: 1301993
Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs.	Heimler A	American journal of medical genetics	1991	PMID: 2063923
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Text-mined citations for rs61750415 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 30, 2024

ClinVar Genomic variation as it relates to human health

NM_000466.3(PEX1):c.2097dup (p.Ile700fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs61750415 ...