NM_000026.4(ADSL):c.1027G>A (p.Glu343Lys) AND Adenylosuccinate lyase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 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:: RCV000810822.8

Allele description [Variation Report for NM_000026.4(ADSL):c.1027G>A (p.Glu343Lys)]

NM_000026.4(ADSL):c.1027G>A (p.Glu343Lys)

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.1027G>A (p.Glu343Lys)

HGVS:

NC_000022.11:g.40362997G>A
NG_007993.2:g.21498G>A
NM_000026.4:c.1027G>AMANE SELECT
NM_001123378.3:c.1027G>A
NM_001317923.2:c.835G>A
NM_001363840.3:c.1027G>A
NP_000017.1:p.Glu343Lys
NP_001116850.1:p.Glu343Lys
NP_001304852.1:p.Glu279Lys
NP_001350769.1:p.Glu343Lys
NC_000022.10:g.40759001G>A
NM_000026.2:c.1027G>A
NR_134256.2:n.1117G>A
p.E343K

Protein change:

E279K

Links:

dbSNP: rs774159147

NCBI 1000 Genomes Browser:

rs774159147

Molecular consequence:

NM_000026.4:c.1027G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001123378.3:c.1027G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317923.2:c.835G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363840.3:c.1027G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134256.2:n.1117G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

mutation affecting coding sequence [Sequence Ontology: SO:1000054]

Condition(s)

Name:: Adenylosuccinate lyase deficiency (ADSLD)
Synonyms:: ADSL DEFICIENCY
Identifiers:: MONDO: MONDO:0007068; MedGen: C0268126; Orphanet: 46; OMIM: 103050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000951057	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001431004	Molecular Genetics Laboratory, Edith Wolfson Medical Center	no assertion criteria provided	Likely pathogenic (Mar 1, 2020)	inherited	in vitro

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000951057

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 2, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001431004

Molecular Genetics Laboratory, Edith Wolfson Medical Center

no assertion criteria provided

Likely pathogenic
(Mar 1, 2020)

inherited

in vitro

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
Caucasian	inherited	yes	1	not provided	not provided	not provided	not provided	in vitro

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000951057.3

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

Description

This sequence change replaces glutamic acid with lysine at codon 343 of the ADSL protein (p.Glu343Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs774159147, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with ADSL-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

#	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 Molecular Genetics Laboratory, Edith Wolfson Medical Center, SCV001431004.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	1	not provided	not provided	in vitro	not provided

Description

Whole Exome Sequencing revealed a novel homozygous variant in the ADSL gene: c.1027G>A ; (p.E343K), inherited from each heterozygous parent. There was a marked elevation of urine succinyladenosine (S-Ado), confirming the diagnosis of ADSL deficiency. In conclusion: Myoclonic tremor status expands the spectrum of movement disorders seen in Adenylosuccinate Lyase deficiency.

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

Last Updated: Apr 13, 2025

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