NM_001182.5(ALDH7A1):c.1279G>C (p.Glu427Gln) AND Seizure

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 13, 2014
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000718443.4

Allele description [Variation Report for NM_001182.5(ALDH7A1):c.1279G>C (p.Glu427Gln)]

NM_001182.5(ALDH7A1):c.1279G>C (p.Glu427Gln)

Gene:

ALDH7A1:aldehyde dehydrogenase 7 family member A1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q23.2

Genomic location:

Preferred name:

NM_001182.5(ALDH7A1):c.1279G>C (p.Glu427Gln)

Other names:

p.E427Q:GAG>CAG; NM_001182.5(ALDH7A1):c.1279G>C

HGVS:

NC_000005.10:g.126552059C>G
NG_008600.3:g.48332G>C
NM_001182.5:c.1279G>CMANE SELECT
NM_001201377.2:c.1195G>C
NM_001202404.2:c.1087G>C
NP_001173.2:p.Glu427Gln
NP_001188306.1:p.Glu399Gln
NP_001189333.2:p.Glu363Gln
NC_000005.9:g.125887751C>G
NG_008600.2:g.48332G>C
NM_001182.3:c.1279G>C
NM_001182.4:c.1279G>C
NM_001201377.1:c.1195G>C
P49419:p.Glu427Gln

Protein change:

E363Q; GLU399GLN

Links:

UniProtKB: P49419#VAR_031719; OMIM: 107323.0001; dbSNP: rs121912707

NCBI 1000 Genomes Browser:

rs121912707

Molecular consequence:

NM_001182.5:c.1279G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001201377.2:c.1195G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001202404.2:c.1087G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Seizure
Synonyms:: Seizures
Identifiers:: MedGen: C0036572; Human Phenotype Ontology: HP:0001250

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000849306	Ambry Genetics	criteria provided, single submitter (Ambry Autosomal Dominant and X-Linked criteria (10/2015))	Pathogenic (Aug 13, 2014)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16491085, 17068770, 19128417, 20370816, 22371912, 22784480, 26224730, 29056246 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000849306

Ambry Genetics

criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))

Pathogenic
(Aug 13, 2014)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Mutations in antiquitin in individuals with pyridoxine-dependent seizures.

Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT.

Nat Med. 2006 Mar;12(3):307-9. Epub 2006 Feb 19.

PubMed [citation]

PMID:: 16491085

Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene.

Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C, Hartmann H, Luecke T, di Capua M, Korenke C, Hikel C, Reutershahn E, Freilinger M, Baumeister F, Bosch F, Erwa W.

Hum Mutat. 2007 Jan;28(1):19-26.

PubMed [citation]

PMID:: 17068770

See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000849306.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (8)

Description

The p.E427Q pathogenic mutation (also known as c.1279G>C), located in coding exon 14 of the ALDH7A1 gene, results from a G to C substitution at nucleotide position 1279. The glutamic acid at codon 427 is replaced by glutamine, an amino acid with highly similar properties. This mutation has been described in numerous unrelated individuals with pyroxidine-dependent seizures in both homozygous and compound heterozygous states, and is reported to be the most common ALDH7A1 mutation, accounting for approximately 30% of mutant alleles (Mills PB et al. Nat. Med., 2006 Mar;12:307-9; Plecko B et al. Hum. Mutat., 2007 Jan;28:19-26; Bennett CL et al. Epilepsia, 2009 May;50:1167-75; Nam SH et al. Ann. Clin. Lab. Sci., 2012;42:65-72; Mefford HC et al. Neurology, 2015 Sep;85:756-62; Butler KM et al. Pediatr. Neurol., 2017 Dec;77:61-66). Enzyme activity in transfected CHO cells and E. coli cells have demonstrated undetectable or extremely low (<3% of WT) enzyme activity (Mills PB et al. Nat. Med., 2006 Mar;12:307-9; Coulter-Mackie MB et al. Mol. Genet. Metab., 2012 Aug;106:478-81). In addition, this alteration is predicted to be probably damaging, deleterious, and deleterious by PolyPhen and SIFT in silico analyses, respectively.Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 13, 2024

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