NM_000018.4(ACADVL):c.1913C>T (p.Ser638Phe) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 29, 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:: RCV001938060.5

Allele description [Variation Report for NM_000018.4(ACADVL):c.1913C>T (p.Ser638Phe)]

NM_000018.4(ACADVL):c.1913C>T (p.Ser638Phe)

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.1913C>T (p.Ser638Phe)

HGVS:

NC_000017.11:g.7225042C>T
NG_007975.1:g.10209C>T
NG_008391.2:g.9G>A
NG_033038.1:g.14503G>A
NM_000018.4:c.1913C>TMANE SELECT
NM_001033859.3:c.1847C>T
NM_001270447.2:c.1982C>T
NM_001270448.2:c.1685C>T
NP_000009.1:p.Ser638Phe
NP_001029031.1:p.Ser616Phe
NP_001257376.1:p.Ser661Phe
NP_001257377.1:p.Ser562Phe
NC_000017.10:g.7128361C>T

Protein change:

S562F

Links:

dbSNP: rs1210477732

NCBI 1000 Genomes Browser:

rs1210477732

Molecular consequence:

NM_000018.4:c.1913C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.1847C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.1685C>T - 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
SCV002184809	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 6, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004563733	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Nov 29, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002184809

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 6, 2021)

germline

clinical testing

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

SCV004563733

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Nov 29, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV002184809.3

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

Description

This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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 serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 638 of the ACADVL protein (p.Ser638Phe). This variant is not present in population databases (gnomAD no frequency).

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004563733.1

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

Description

The ACADVL c.1913C>T; p.Ser638Phe variant (rs1210477732), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1408497). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.81). Due to limited information, the clinical significance of this variant is uncertain at this time.

#	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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