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NM_000017.4(ACADS):c.136C>T (p.Arg46Trp) AND ACADS-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 19, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003398440.5

Allele description [Variation Report for NM_000017.4(ACADS):c.136C>T (p.Arg46Trp)]

NM_000017.4(ACADS):c.136C>T (p.Arg46Trp)

Gene:
ACADS:acyl-CoA dehydrogenase short chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.31
Genomic location:
Preferred name:
NM_000017.4(ACADS):c.136C>T (p.Arg46Trp)
Other names:
p.R46W:CGG>TGG
HGVS:
  • NC_000012.12:g.120727115C>T
  • NG_007991.1:g.6348C>T
  • NM_000017.4:c.136C>TMANE SELECT
  • NM_001302554.2:c.136C>T
  • NP_000008.1:p.Arg46Trp
  • NP_001289483.1:p.Arg46Trp
  • NC_000012.11:g.121164918C>T
  • NM_000017.2:c.136C>T
  • NM_000017.3:c.136C>T
  • P16219:p.Arg46Trp
Protein change:
R46W; ARG46TRP
Links:
UniProtKB: P16219#VAR_000310; OMIM: 606885.0001; dbSNP: rs121908003
NCBI 1000 Genomes Browser:
rs121908003
Molecular consequence:
  • NM_000017.4:c.136C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001302554.2:c.136C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
ACADS-related disorder
Synonyms:
ACADS-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004120760PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Aug 19, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004120760.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ACADS c.136C>T variant is predicted to result in the amino acid substitution p.Arg46Trp. This variant was previously referred to as R22W in the literature. This variant has been reported in the homozygous or compound heterozygous state in patients with short chain acyl-CoA-dehydrogenase deficiency (Corydon et al. 1998. PubMed ID: 9582344; Alfares et al. 2017. PubMed ID: 28454995; Messina M et al. 2020. PubMed ID: 33239584). In experimental studies, the p.Arg46Trp substitution has been shown to result in decreased enzyme activity as well as affecting protein folding, increased protein aggregation, and more rapid degradation than wild-type (Corydon et al. 1998. PubMed ID: 9582344; Pedersen et al. 2003. PubMed ID: 14506246). The c.136C>T variant has been reported at a maximum allele frequency of ~0.08% in a large population database, indicating it is rare in the general population. In summary, we classify this variant as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024