NM_000026.4(ADSL):c.1277G>A (p.Arg426His) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 2, 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:: RCV002512680.2

Allele description [Variation Report for NM_000026.4(ADSL):c.1277G>A (p.Arg426His)]

NM_000026.4(ADSL):c.1277G>A (p.Arg426His)

Gene:

ADSL:adenylosuccinate lyase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.1

Genomic location:

Preferred name:

NM_000026.4(ADSL):c.1277G>A (p.Arg426His)

Other names:

p.R426H:CGT>CAT

HGVS:

NC_000022.11:g.40364965G>A
NG_007993.2:g.23466G>A
NM_000026.4:c.1277G>AMANE SELECT
NM_001123378.3:c.1191+600G>A
NM_001317923.2:c.1085G>A
NM_001363840.3:c.1277G>A
NP_000017.1:p.Arg426His
NP_001304852.1:p.Arg362His
NP_001350769.1:p.Arg426His
NC_000022.10:g.40760969G>A
NM_000026.2:c.1277G>A
NM_000026.3:c.1277G>A
NR_134256.2:n.1367G>A
P30566:p.Arg426His

Protein change:

R362H; ARG426HIS

Links:

UniProtKB: P30566#VAR_007978; OMIM: 608222.0002; dbSNP: rs119450941

NCBI 1000 Genomes Browser:

rs119450941

Molecular consequence:

NM_001123378.3:c.1191+600G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000026.4:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317923.2:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363840.3:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134256.2:n.1367G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003677029	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 2, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10888601, 20127976, 22180458, 23504561, 23714113, 27504266, 33648541 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003677029

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 2, 2021)

germline

clinical testing

PubMed (7)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients.

Kmoch S, Hartmannová H, Stibůrková B, Krijt J, Zikánová M, Sebesta I.

Hum Mol Genet. 2000 Jun 12;9(10):1501-13.

PubMed [citation]

PMID:: 10888601

Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency.

Zikanova M, Skopova V, Hnizda A, Krijt J, Kmoch S.

Hum Mutat. 2010 Apr;31(4):445-55. doi: 10.1002/humu.21212.

PubMed [citation]

PMID:: 20127976

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV003677029.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The c.1277G>A (p.R426H) alteration is located in exon 12 (coding exon 12) of the ADSL gene. This alteration results from a G to A substitution at nucleotide position 1277, causing the arginine (R) at amino acid position 426 to be replaced by a histidine (H). Based on data from the Genome Aggregation Database (gnomAD), the ADSL c.1277G>A alteration was observed in 0.02% (51/282896) of total alleles studied, with a frequency of 0.03% (42/129196) in the European (non-Finnish) subpopulation. This mutation is the most common mutation occurring in about 30% of affected individuals; it has been identified in the homozygous and compound heterozygous state in multiple individuals with adenylosuccinase deficiency (Ray, 2013; Jurecka, 2014; Donti, 2016; Mastrogiorgio, 2021). In vitro analysis demonstrated reduced thermal stability and ADSL activity (Kmoch, 2000; Zikanova, 2010). The p.R426H alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

#	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: Sep 29, 2024

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