NM_000018.4(ACADVL):c.506T>C (p.Met169Thr) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 6, 2022
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:: RCV001063820.9

Allele description [Variation Report for NM_000018.4(ACADVL):c.506T>C (p.Met169Thr)]

NM_000018.4(ACADVL):c.506T>C (p.Met169Thr)

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.506T>C (p.Met169Thr)

HGVS:

NC_000017.11:g.7221566T>C
NG_007975.1:g.6733T>C
NG_008391.2:g.3485A>G
NM_000018.4:c.506T>CMANE SELECT
NM_001033859.3:c.440T>C
NM_001270447.2:c.575T>C
NM_001270448.2:c.278T>C
NP_000009.1:p.Met169Thr
NP_001029031.1:p.Met147Thr
NP_001257376.1:p.Met192Thr
NP_001257377.1:p.Met93Thr
NC_000017.10:g.7124885T>C
NC_000017.10:g.7124885T>C
NM_000018.3:c.506T>C

Protein change:

M147T

Links:

dbSNP: rs1382262076

NCBI 1000 Genomes Browser:

rs1382262076

Molecular consequence:

NM_000018.4:c.506T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.440T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.575T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.278T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Very long chain acyl-CoA dehydrogenase deficiency (ACADVLD)
Synonyms:: VLCAD deficiency
Identifiers:: MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001228683	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 6, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33996489, 28492532
SCV002088753	Natera, Inc.	no assertion criteria provided	Uncertain significance (Mar 20, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001228683

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 6, 2022)

germline

clinical testing

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

SCV002088753

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Mar 20, 2020)

germline

clinical testing

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

The perioperative transition of serum biomarkers of a 1.5-year-old boy with very-long-chain acyl-CoA dehydrogenase deficiency.

Bo R, Awano H, Yamada K, Ooi M, Okata Y, Bitoh Y, Mizobuchi S, Iijima K.

Mol Genet Metab Rep. 2021 Jun;27:100760. doi: 10.1016/j.ymgmr.2021.100760.

PubMed [citation]

PMID:: 33996489
PMCID:: PMC8086129

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001228683.4

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 169 of the ACADVL protein (p.Met169Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with VLCAD deficiency (PMID: 33996489). ClinVar contains an entry for this variant (Variation ID: 858025).

#	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 Natera, Inc., SCV002088753.1

#	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: Sep 29, 2024

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