NM_001182.5(ALDH7A1):c.1549A>T (p.Met517Leu) AND Pyridoxine-dependent epilepsy

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 2021
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:: RCV001932797.5

Allele description

NM_001182.5(ALDH7A1):c.1549A>T (p.Met517Leu)

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.1549A>T (p.Met517Leu)

HGVS:

NC_000005.10:g.126546340T>A
NG_008600.3:g.54051A>T
NM_001182.5:c.1549A>TMANE SELECT
NM_001201377.2:c.1465A>T
NM_001202404.2:c.1357A>T
NP_001173.2:p.Met517Leu
NP_001188306.1:p.Met489Leu
NP_001189333.2:p.Met453Leu
NC_000005.9:g.125882032T>A
NG_008600.2:g.54051A>T

Protein change:

M453L

Links:

dbSNP: rs1749785606

NCBI 1000 Genomes Browser:

rs1749785606

Molecular consequence:

NM_001182.5:c.1549A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001201377.2:c.1465A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001202404.2:c.1357A>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002173253	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002173253

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2021)

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	germline	unknown	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

Details of each submission

From Invitae, SCV002173253.3

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

Description

This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ALDH7A1 protein function. This variant has not been reported in the literature in individuals with ALDH7A1-related conditions. This sequence change replaces methionine with leucine at codon 517 of the ALDH7A1 protein (p.Met517Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine.

#	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: Mar 5, 2024

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