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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001361315	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jun 13, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21932095, 28468868, 26385305, 31031081, 35281659, 34437764 Citation Link,
SCV002516830	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Uncertain significance (May 4, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001361315

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jun 13, 2024)

germline

clinical testing

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

Citation Link,

SCV002516830

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Uncertain significance
(May 4, 2022)

germline

clinical testing

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

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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 Mendelics, SCV002516830.1

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

#	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: Nov 3, 2024

ClinVar

Relating variation to medicine