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

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 21, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001174775.1

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_001033859.3:c.935T>G
NM_001270447.2:c.1070T>G
NM_001270448.2:c.773T>G
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_001033859.3:c.935T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1070T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.773T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001338104	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 21, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26385305, 27209629 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001338104

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 21, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States.

Miller MJ, Burrage LC, Gibson JB, Strenk ME, Lose EJ, Bick DP, Elsea SH, Sutton VR, Sun Q, Graham BH, Craigen WJ, Zhang VW, Wong LJ.

Mol Genet Metab. 2015 Nov;116(3):139-45. doi: 10.1016/j.ymgme.2015.08.011. Epub 2015 Sep 2.

PubMed [citation]

PMID:: 26385305
PMCID:: PMC4790081

Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.

Pena LD, van Calcar SC, Hansen J, Edick MJ, Walsh Vockley C, Leslie N, Cameron C, Mohsen AW, Berry SA, Arnold GL, Vockley J; IBEMC..

Mol Genet Metab. 2016 Aug;118(4):272-81. doi: 10.1016/j.ymgme.2016.05.007. Epub 2016 May 13.

PubMed [citation]

PMID:: 27209629
PMCID:: PMC4970910

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001338104.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: ACADVL c.1001T>G (p.Met334Arg) results in a non-conservative amino acid change located in the Acyl-CoA dehydrogenase/oxidase C-terminal domain 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 1.6e-05 in 251308 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1001T>G has been reported in the literature in individuals affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency following newborn screening results (Miller_2015, Pena_2016). These reports however, do not provide unequivocal conclusions about association of the variant with Very Long Chain Acyl-CoA Dehydrogenase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Jun 18, 2022

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