NM_000466.2(PEX1):c.1991T>C (p.Leu664Pro) AND Zellweger syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jun 5, 2014
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000007949.7

Allele description

NM_000466.2(PEX1):c.1991T>C (p.Leu664Pro)

Gene:

PEX1:peroxisomal biogenesis factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q21.2

Genomic location:

Preferred name:

NM_000466.2(PEX1):c.1991T>C (p.Leu664Pro)

HGVS:

NC_000007.14:g.92504812A>G
NG_008341.1:g.28720T>C
NM_000466.2:c.1991T>C
NM_001282677.1:c.1900+1436T>C
NP_000457.1:p.Leu664Pro
NC_000007.13:g.92134126A>G
O43933:p.Leu664Pro

Protein change:

L664P; LEU664PRO

Links:

UniProtKB: O43933#VAR_008876; OMIM: 602136.0002; dbSNP: rs121434455

NCBI 1000 Genomes Browser:

rs121434455

Molecular consequence:

NM_001282677.1:c.1900+1436T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000466.2:c.1991T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Zellweger syndrome (ZS)
Synonyms:: Peroxisome biogenesis disorder 1A (Zellweger); Peroxisome biogenesis disorder 1a
Identifiers:: MedGen: C0043459; Orphanet: 912; OMIM: 214100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028154	OMIM	no assertion criteria provided	Pathogenic (Apr 14, 1998)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000220370	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jun 5, 2014)	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 11439091, 9539740 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015) Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028154

OMIM

no assertion criteria provided

Pathogenic
(Apr 14, 1998)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000220370

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Jun 5, 2014)

unknown

literature only

PubMed (2)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction.

Tamura S, Matsumoto N, Imamura A, Shimozawa N, Suzuki Y, Kondo N, Fujiki Y.

Biochem J. 2001 Jul 15;357(Pt 2):417-26.

PubMed [citation]

PMID:: 11439091
PMCID:: PMC1221968

Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.

Tamura S, Okumoto K, Toyama R, Shimozawa N, Tsukamoto T, Suzuki Y, Osumi T, Kondo N, Fujiki Y.

Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4350-5.

PubMed [citation]

PMID:: 9539740
PMCID:: PMC22492

Details of each submission

From OMIM, SCV000028154.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with Zellweger syndrome of complementation group 1 (PBD1A; 214100), Tamura et al. (1998) identified compound heterozygosity for a 1191T-C mutation in the PEX1 gene, resulting in an leu664-to-pro (L664P) substitution, and a 171-bp deletion of nucleotide residues 1,900 to 2,070 (602136.0003). Northern blot analysis of patient and control mRNA revealed a 4.3-kb band in both, suggesting that PEX1 transcription was unaffected in the patient. Functional analysis demonstrated that cDNAs corresponding to both PEX1 mutations were defective in peroxisome-restoring activity when expressed in the patient's fibroblasts as well as in ZP107 cells.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000220370.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 6, 2018

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