NM_000018.4(ACADVL):c.520G>A (p.Val174Met) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 19, 2023
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:: RCV000077919.21

Allele description [Variation Report for NM_000018.4(ACADVL):c.520G>A (p.Val174Met)]

NM_000018.4(ACADVL):c.520G>A (p.Val174Met)

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.520G>A (p.Val174Met)

HGVS:

NC_000017.11:g.7221580G>A
NG_007975.1:g.6747G>A
NG_008391.2:g.3471C>T
NM_000018.4:c.520G>AMANE SELECT
NM_001033859.3:c.454G>A
NM_001270447.2:c.589G>A
NM_001270448.2:c.292G>A
NP_000009.1:p.Val174Met
NP_000009.1:p.Val174Met
NP_001029031.1:p.Val152Met
NP_001257376.1:p.Val197Met
NP_001257377.1:p.Val98Met
NP_001257377.1:p.Val98Met
NC_000017.10:g.7124899G>A
NM_000018.2:c.520G>A
NM_000018.3:c.520G>A
NM_000018.4:c.520G>A
NM_001270448.1:c.292G>A
P49748:p.Val174Met

Protein change:

V152M

Links:

UniProtKB: P49748#VAR_000334; dbSNP: rs369560930

NCBI 1000 Genomes Browser:

rs369560930

Molecular consequence:

NM_000018.4:c.520G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.454G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.589G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.292G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000231986	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Mar 23, 2015)	germline	clinical testing	Citation Link,
SCV000518399	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Sep 26, 2017)	germline	clinical testing	Citation Link,
SCV004226686	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 19, 2023)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 17999356, 18670371, 20060901, 23430950, 26881790, 28755359, 30194637, 35281663, 36078043, 9973285, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000231986

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions)

Pathogenic
(Mar 23, 2015)

germline

clinical testing

Citation Link,

SCV000518399

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Sep 26, 2017)

germline

clinical testing

Citation Link,

SCV004226686

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 19, 2023)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	5	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.

Gobin-Limballe S, Djouadi F, Aubey F, Olpin S, Andresen BS, Yamaguchi S, Mandel H, Fukao T, Ruiter JP, Wanders RJ, McAndrew R, Kim JJ, Bastin J.

Am J Hum Genet. 2007 Dec;81(6):1133-43. Epub 2007 Oct 29.

PubMed [citation]

PMID:: 17999356
PMCID:: PMC2276345

Development of a new enzymatic diagnosis method for very-long-chain Acyl-CoA dehydrogenase deficiency by detecting 2-hexadecenoyl-CoA production and its application in tandem mass spectrometry-based selective screening and newborn screening in Japan.

Tajima G, Sakura N, Shirao K, Okada S, Tsumura M, Nishimura Y, Ono H, Hasegawa Y, Hata I, Naito E, Yamaguchi S, Shigematsu Y, Kobayashi M.

Pediatr Res. 2008 Dec;64(6):667-72. doi: 10.1203/PDR.0b013e318187cc44.

PubMed [citation]

PMID:: 18670371

See all PubMed Citations (11)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000231986.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	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		4	not provided	not provided	not provided

From GeneDx, SCV000518399.4

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

Description

The V174M missense variant has been previously reported in association with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (Tajima et al., 2008; Gobin-Limballe et al., 2010; Andresen et al., 1999). V174M is reported to likely be a mild ACADVL variant as fibroblasts homozygous for V174M showed enzyme activity equivalent to 27% of normal levels (Gobin-Limballe et al., 2010). The V174M variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The V174M substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, we interpret V174M as likely pathogenic.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226686.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (11)

Description

PP4, PM2, PM3_strong, PS3

#	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		1	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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