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NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp) AND not specified

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jun 13, 2024
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:
RCV001192883.14

Allele description [Variation Report for NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)]

NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)

Gene:
ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)
HGVS:
  • NC_000017.11:g.7224379C>T
  • NG_007975.1:g.9546C>T
  • NG_008391.2:g.672G>A
  • NG_033038.1:g.15166G>A
  • NM_000018.4:c.1591C>TMANE SELECT
  • NM_001033859.3:c.1525C>T
  • NM_001270447.2:c.1660C>T
  • NM_001270448.2:c.1363C>T
  • NP_000009.1:p.Arg531Trp
  • NP_000009.1:p.Arg531Trp
  • NP_001029031.1:p.Arg509Trp
  • NP_001257376.1:p.Arg554Trp
  • NP_001257377.1:p.Arg455Trp
  • NP_001257377.1:p.Arg455Trp
  • NC_000017.10:g.7127698C>T
  • NM_000018.2:c.1591C>T
  • NM_000018.3:c.1591C>T
  • NM_001270448.1:c.1363C>T
Protein change:
R455W
Links:
dbSNP: rs146379816
NCBI 1000 Genomes Browser:
rs146379816
Molecular consequence:
  • NM_000018.4:c.1591C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001033859.3:c.1525C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270447.2:c.1660C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270448.2:c.1363C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001361315Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Jun 13, 2024) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV002516830Mendelics
criteria provided, single submitter

(Mendelics Assertion Criteria 2019)		Uncertain significance
(May 4, 2022) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

VLCAD enzyme activity determinations in newborns identified by screening: a valuable tool for risk assessment.

Hoffmann L, Haussmann U, Mueller M, Spiekerkoetter U.

J Inherit Metab Dis. 2012 Mar;35(2):269-77. doi: 10.1007/s10545-011-9391-8. Epub 2011 Sep 20.

PubMed [citation]
PMID:
21932095

Diagnosing childhood-onset inborn errors of metabolism by next-generation sequencing.

Ghosh A, Schlecht H, Heptinstall LE, Bassett JK, Cartwright E, Bhaskar SS, Urquhart J, Broomfield A, Morris AA, Jameson E, Schwahn BC, Walter JH, Douzgou S, Murphy H, Hendriksz C, Sharma R, Wilcox G, Crushell E, Monavari AA, Martin R, Doolan A, Senniappan S, et al.

Arch Dis Child. 2017 Nov;102(11):1019-1029. doi: 10.1136/archdischild-2017-312738. Epub 2017 May 3.

PubMed [citation]
PMID:
28468868
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361315.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: ACADVL c.1591C>T (p.Arg531Trp) results in a non-conservative amino acid change located in the ACAD9/ACADV-like, C-terminal domain (IPR049448) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00044 in 250116 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in ACADVL causing Very Long Chain Acyl-CoA Dehydrogenase Deficiency (0.00044 vs 0.0029), allowing no conclusion about variant significance. c.1591C>T has been reported in the literature as a biallelic genotype in individuals affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency (e.g. Hoffmann_2012, Rovelli_2019, Olsson_2022). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21932095, 28468868, 26385305, 31031081, 35281659, 34437764). ClinVar contains an entry for this variant (Variation ID: 166647). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

From Mendelics, SCV002516830.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024