NM_001182.5(ALDH7A1):c.91_92del (p.Thr31fs) AND Pyridoxine-dependent epilepsy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 16, 2023
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:: RCV001231545.5

Allele description [Variation Report for NM_001182.5(ALDH7A1):c.91_92del (p.Thr31fs)]

NM_001182.5(ALDH7A1):c.91_92del (p.Thr31fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

5q23.2

Genomic location:

Preferred name:

NM_001182.5(ALDH7A1):c.91_92del (p.Thr31fs)

HGVS:

NC_000005.10:g.126595108_126595109del
NG_008600.3:g.5283_5284del
NM_001182.5:c.91_92delMANE SELECT
NM_001201377.2:c.7_8del
NM_001202404.2:c.91_92del
NP_001173.2:p.Thr31fs
NP_001188306.1:p.Thr3fs
NP_001189333.2:p.Thr31fs
NC_000005.9:g.125930799_125930800del
NC_000005.9:g.125930800_125930801del
NG_008600.2:g.5283_5284del
NM_001182.4:c.91_92del

Protein change:

T31fs

Links:

dbSNP: rs1751700395

NCBI 1000 Genomes Browser:

rs1751700395

Molecular consequence:

NM_001182.5:c.91_92del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001201377.2:c.7_8del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001202404.2:c.91_92del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Pyridoxine-dependent epilepsy (EPEO4)
Synonyms:: Pyridoxine dependency; Pyridoxine dependency with seizures; Vitamin B6-dependent seizures; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009945; MedGen: C1849508; Orphanet: 3006; OMIM: 266100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001404071	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 16, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16491085, 20554659, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001404071

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 16, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency).

Mills PB, Footitt EJ, Mills KA, Tuschl K, Aylett S, Varadkar S, Hemingway C, Marlow N, Rennie J, Baxter P, Dulac O, Nabbout R, Craigen WJ, Schmitt B, Feillet F, Christensen E, De Lonlay P, Pike MG, Hughes MI, Struys EA, Jakobs C, Zuberi SM, et al.

Brain. 2010 Jul;133(Pt 7):2148-59. doi: 10.1093/brain/awq143. Epub 2010 Jun 16.

PubMed [citation]

PMID:: 20554659
PMCID:: PMC2892945

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001404071.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 958387). This variant has not been reported in the literature in individuals affected with ALDH7A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr31Serfs*25) in the ALDH7A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALDH7A1 are known to be pathogenic (PMID: 16491085, 20554659).

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

Last Updated: Feb 28, 2024

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