NM_000018.4(ACADVL):c.1001T>G (p.Met334Arg) AND not provided

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

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Apr 18, 2018
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:: RCV000077898.9

Allele description

NM_000018.4(ACADVL):c.1001T>G (p.Met334Arg)

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.1001T>G (p.Met334Arg)

Other names:

p.M334R:ATG>AGG

HGVS:

NC_000017.11:g.7222789T>G
NG_007975.1:g.7956T>G
NG_008391.2:g.2262A>C
NM_000018.4:c.1001T>GMANE SELECT
NM_001033859.2:c.935T>G
NM_001270447.1:c.1070T>G
NM_001270448.1:c.773T>G
NP_000009.1:p.Met334Arg
NP_000009.1:p.Met334Arg
NP_000009.1:p.Met334Arg
NP_001029031.1:p.Met312Arg
NP_001257376.1:p.Met357Arg
NP_001257377.1:p.Met258Arg
NC_000017.10:g.7126108T>G
NM_000018.2:c.1001T>G
NM_000018.3:c.1001T>G
NM_001033859.1:c.935T>G

Protein change:

M258R

Links:

dbSNP: rs398123079

NCBI 1000 Genomes Browser:

rs398123079

Molecular consequence:

NM_000018.4:c.1001T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.2:c.935T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.1:c.1070T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.1:c.773T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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
SCV000109727	EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Jul 2, 2015)	germline	clinical testing	Citation Link,
SCV000238642	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Apr 18, 2018)	germline	clinical testing	Citation Link,
SCV000280923	Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Feb 19, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000109727

EGL Genetic Diagnostics, Eurofins Clinical Diagnostics

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Jul 2, 2015)

germline

clinical testing

Citation Link,

SCV000238642

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Apr 18, 2018)

germline

clinical testing

Citation Link,

SCV000280923

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Feb 19, 2015)

germline

clinical testing

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

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	2	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, SCV000109727.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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		2	not provided	not provided	not provided

From GeneDx, SCV000238642.13

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

Description

The M334R variant has been reported in multiple individuals with an abnormal newborn screening result for VLCAD deficiency in whom a second ACADVL variant was not identified (Miller et al. 2015). M334R has also been reported in an asymptomatic individual who was diagnosed with VLCAD deficiency via molecular testing and acylcarnitine profile analysis following an abnormal newborn screening result. This individual also had a second missense variant identified in the ACADVL gene although the phase of the two variants was not reported (Pena et al., 2016) The M334R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). M334R is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, based on the currently available information, it is unclear whether the M334R variant pathogenic or a rare benign variant.

#	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 Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000280923.1

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

Description

Converted during submission to Uncertain significance.

#	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	0.000112	not provided	not provided

Last Updated: Sep 26, 2021

ClinVar

Relating variation to medicine