NM_000018.4(ACADVL):c.664G>A (p.Gly222Arg) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Aug 31, 2017
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:: RCV000077922.7

Allele description

NM_000018.4(ACADVL):c.664G>A (p.Gly222Arg)

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.664G>A (p.Gly222Arg)

HGVS:

NC_000017.11:g.7221993G>A
NG_007975.1:g.7160G>A
NG_008391.2:g.3058C>T
NM_000018.4:c.664G>AMANE SELECT
NM_001033859.2:c.598G>A
NM_001270447.1:c.733G>A
NM_001270448.1:c.436G>A
NP_000009.1:p.Gly222Arg
NP_000009.1:p.Gly222Arg
NP_000009.1:p.Gly222Arg
NP_001029031.1:p.Gly200Arg
NP_001257376.1:p.Gly245Arg
NP_001257377.1:p.Gly146Arg
NC_000017.10:g.7125312G>A
NM_000018.2:c.664G>A
NM_000018.3:c.664G>A

Protein change:

G146R

Links:

dbSNP: rs398123091

NCBI 1000 Genomes Browser:

rs398123091

Molecular consequence:

NM_000018.4:c.664G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.2:c.598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.1:c.733G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.1:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000109751	EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely pathogenic (Aug 31, 2017)	germline	clinical testing	Citation Link,
SCV000281258	Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 27, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000491232	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Nov 22, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000109751

EGL Genetic Diagnostics, Eurofins Clinical Diagnostics

criteria provided, single submitter

(EGL Classification Definitions 2015)

Likely pathogenic
(Aug 31, 2017)

germline

clinical testing

Citation Link,

SCV000281258

Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 27, 2014)

germline

clinical testing

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

SCV000491232

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Nov 22, 2016)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000109751.8

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

From Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000281258.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	0.000224	not provided	not provided

From GeneDx, SCV000491232.1

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

Description

The G222R missense variant in the ACADVL gene has been reported previously in patients with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (Voermans et al. 2006; Gobin-Limballe et al. 2007; Li et al. 2015). The G222R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G222R variant is a non-conservative amino acid substitution, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, G222 is the first residue of the conserved Gly-Ser-Asp segment where it is believed that substitution of Glycine by a bulky, charged Arginine may change the conformation of the VLCAD protein and disrupt cofactor binding (Gobin-Limballe et al. 2010). In summary, we interpret G222R to be 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

Last Updated: Sep 26, 2021

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