NM_001182.5(ALDH7A1):c.373A>G (p.Ile125Val) AND Pyridoxine-dependent epilepsy

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Feb 2, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000204650.30

Allele description [Variation Report for NM_001182.5(ALDH7A1):c.373A>G (p.Ile125Val)]

NM_001182.5(ALDH7A1):c.373A>G (p.Ile125Val)

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.373A>G (p.Ile125Val)

Other names:

p.I125V:ATC>GTC

HGVS:

NC_000005.10:g.126583952T>C
NG_008600.2:g.16439A>G
NM_001182.5:c.373A>GMANE SELECT
NM_001201377.2:c.289A>G
NM_001202404.2:c.373A>G
NP_001173.2:p.Ile125Val
NP_001188306.1:p.Ile97Val
NP_001189333.2:p.Ile125Val
NC_000005.9:g.125919644T>C
NM_001182.3:c.373A>G
NM_001182.4:c.373A>G

Protein change:

I125V

Links:

dbSNP: rs117295656

NCBI 1000 Genomes Browser:

rs117295656

Molecular consequence:

NM_001182.5:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001201377.2:c.289A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001202404.2:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Pyridoxine-dependent epilepsy (EPEO4)
Synonyms:: PYRIDOXINE DEPENDENCY WITH SEIZURES; EPILEPSY, EARLY-ONSET, 4, VITAMIN B6-DEPENDENT; Pyridoxine-Dependent Seizures
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
SCV000260348	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 2, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000452313	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV002797222	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Apr 4, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004049849	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000260348.12

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

#	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

From Illumina Laboratory Services, Illumina, SCV000452313.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002797222.1

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

#	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

From Genome-Nilou Lab, SCV004049849.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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