NM_000018.4(ACADVL):c.1063_1064delinsGG (p.Ile355Gly) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 30, 2021
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:: RCV002870910.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.1063_1064delinsGG (p.Ile355Gly)]

NM_000018.4(ACADVL):c.1063_1064delinsGG (p.Ile355Gly)

Gene:

ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.1063_1064delinsGG (p.Ile355Gly)

HGVS:

NC_000017.11:g.7222851_7222852delinsGG
NG_007975.1:g.8018_8019delinsGG
NG_008391.2:g.2199_2200delinsCC
NG_008391.3:g.2198_2199delinsCC
NM_000018.4:c.1063_1064delinsGGMANE SELECT
NM_001033859.3:c.997_998delinsGG
NM_001270447.2:c.1132_1133delinsGG
NM_001270448.2:c.835_836delinsGG
NP_000009.1:p.Ile355Gly
NP_001029031.1:p.Ile333Gly
NP_001257376.1:p.Ile378Gly
NP_001257377.1:p.Ile279Gly
NC_000017.10:g.7126170_7126171delinsGG

Protein change:

I279G

Molecular consequence:

NM_000018.4:c.1063_1064delinsGG - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.997_998delinsGG - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1132_1133delinsGG - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.835_836delinsGG - 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
SCV003223440	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 30, 2021)	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

SCV003223440

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 30, 2021)

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	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, SCV003223440.1

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 355 of the ACADVL protein (p.Ile355Gly). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). This variant disrupts the p.Ile355 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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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