ClinVar Genomic variation as it relates to human health
NM_000018.4(ACADVL):c.605T>A (p.Leu202His)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Likely pathogenic(1); Uncertain significance(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000018.4(ACADVL):c.605T>A (p.Leu202His)
Variation ID: 92287 Accession: VCV000092287.15
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17p13.1 17: 7221665 (GRCh38) [ NCBI UCSC ] 17: 7124984 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 29, 2015 Feb 4, 2024 Dec 6, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000018.4:c.605T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000009.1:p.Leu202His missense NM_001033859.3:c.539T>A NP_001029031.1:p.Leu180His missense NM_001270447.2:c.674T>A NP_001257376.1:p.Leu225His missense NM_001270448.2:c.377T>A NP_001257377.1:p.Leu126His missense NC_000017.11:g.7221665T>A NC_000017.10:g.7124984T>A NG_007975.1:g.6832T>A NG_008391.2:g.3386A>T - Protein change
- L202H, L180H, L126H, L225H
- Other names
- -
- Canonical SPDI
- NC_000017.11:7221664:T:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
ACADVL | - | - |
GRCh38 GRCh37 |
1704 | 1909 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Uncertain significance (1) |
criteria provided, single submitter
|
Dec 6, 2012 | RCV000077920.15 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Dec 6, 2023 | RCV001001444.17 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Uncertain significance
(Dec 06, 2012)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000109749.8
First in ClinVar: Jan 17, 2014 Last updated: Jun 29, 2015 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Uncertain significance
(Nov 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
|
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV001365035.2
First in ClinVar: Jul 16, 2020 Last updated: Jul 16, 2020 |
Comment:
The NM_000018.3:c.605T>A (NP_000009.1:p.Leu202His) [GRCH38: NC_000017.11:g.7221665T>A] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been … (more)
The NM_000018.3:c.605T>A (NP_000009.1:p.Leu202His) [GRCH38: NC_000017.11:g.7221665T>A] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PP3 (less)
|
|
Likely pathogenic
(Dec 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004241864.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
Variant summary: ACADVL c.605T>A (p.Leu202His) results in a non-conservative amino acid change located in the N-terminal domain (IPR013786) of the encoded protein sequence. Five of … (more)
Variant summary: ACADVL c.605T>A (p.Leu202His) results in a non-conservative amino acid change located in the N-terminal domain (IPR013786) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251270 control chromosomes (gnomAD). c.605T>A has been reported in the literature in individuals affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency (e.g. Miller_2015, Rovelli_2019, Ambrose_2022). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However other missense variants affecting the same amino acid have been reported in affected individuals (HGMD) and been classified as pathogenic by other laboratories in ClinVar, suggesting that this residue is critical for protein function. The following publications have been ascertained in the context of this evaluation (PMID: 26385305, 31031081, 36109795). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
|
|
Uncertain significance
(Sep 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001158682.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The ACADVL c.605T>A; p.Leu202His variant (rs398123090), to our knowledge, is not reported in the medical literature but is reported as uncertain significance in ClinVar (Variation … (more)
The ACADVL c.605T>A; p.Leu202His variant (rs398123090), to our knowledge, is not reported in the medical literature but is reported as uncertain significance in ClinVar (Variation ID: 92287). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The leucine at codon 202 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Leu202His variant is uncertain at this time. (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Outcomes of mitochondrial long chain fatty acid oxidation and carnitine defects from a single center metabolic genetics clinic. | Ambrose A | Orphanet journal of rare diseases | 2022 | PMID: 36109795 |
Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency. | Rovelli V | Molecular genetics and metabolism | 2019 | PMID: 31031081 |
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 | Molecular genetics and metabolism | 2015 | PMID: 26385305 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADVL | - | - | - | - |
Text-mined citations for rs398123090 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.