ClinVar Genomic variation as it relates to human health
NM_000018.4(ACADVL):c.890AGA[2] (p.Lys299del)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000018.4(ACADVL):c.890AGA[2] (p.Lys299del)
Variation ID: 92292 Accession: VCV000092292.29
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 17p13.1 17: 7222678-7222680 (GRCh38) [ NCBI UCSC ] 17: 7125997-7125999 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 29, 2015 Jun 17, 2024 Jan 8, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000018.4:c.890AGA[2] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000009.1:p.Lys299del inframe deletion NM_000018.4:c.896_898del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000018.4:c.896_898delAGA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000018.2:c.896_898delAGA NP_000009.1:p.Lys299del NM_000018.3:c.896_898del NM_001033859.3:c.824AGA[2] NP_001029031.1:p.Lys277del inframe deletion NM_001270447.2:c.959AGA[2] NP_001257376.1:p.Lys322del inframe deletion NM_001270448.1:c.668_670delAGA NM_001270448.2:c.662AGA[2] NP_001257377.1:p.Lys223del inframe deletion NC_000017.11:g.7222678AGA[2] NC_000017.10:g.7125997AGA[2] NG_007975.1:g.7845AGA[2] NG_008391.2:g.2365TCT[2] - Protein change
- K299del, K223del, K277del, K322del
- Other names
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- Canonical SPDI
- NC_000017.11:7222677:AGAAGAAGA:AGAAGA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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ACADVL | - | - |
GRCh38 GRCh37 |
1717 | 1925 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Jan 8, 2024 | RCV000001694.31 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 19, 2021 | RCV000077926.25 |
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
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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. |
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Pathogenic
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004222934.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
Variant summary: ACADVL c.896_898delAGA (p.Lys299del) results in an in-frame deletion that is predicted to remove one amino acids from the encoded protein. The variant allele … (more)
Variant summary: ACADVL c.896_898delAGA (p.Lys299del) results in an in-frame deletion that is predicted to remove one amino acids from the encoded protein. The variant allele was found at a frequency of 2.4e-05 in 250448 control chromosomes (gnomAD). c.896_898delAGA (also known as c.895_897del and K258del) has been reported in the literature in multiple individuals affected with features of Very Long Chain Acyl-CoA Dehydrogenase Deficiency (examples: Souri_1996, Mathur_1999, Lin_2020, Wang_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence that this variant disrupts normal protein activity (Souri_1996). The following publications have been ascertained in the context of this evaluation (PMID: 8554073, 32710939, 10077518, 33278787). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jan 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000654974.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This variant, c.896_898del, results in the deletion of 1 amino acid(s) of the ACADVL protein (p.Lys299del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.896_898del, results in the deletion of 1 amino acid(s) of the ACADVL protein (p.Lys299del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs761162357, gnomAD 0.008%). This variant has been observed in individual(s) with clinical features of very-long-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 8554073, 10738914; Invitae). This variant is also known as c.895_897del and K258del. ClinVar contains an entry for this variant (Variation ID: 92292). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ACADVL function (PMID: 8554073). This variant disrupts the p.Lys299 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been observed in individuals with ACADVL-related conditions (PMID: 9973285, 16982043), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004215947.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(May 15, 2013)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000224740.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Nov 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV001364909.2
First in ClinVar: Jul 16, 2020 Last updated: Jul 16, 2020 |
Comment:
The NM_000018.3:c.896_898delAGA (NP_000009.1:p.Lys299del) [GRCH38: NC_000017.11:g.7222684_7222686delAGA] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported … (more)
The NM_000018.3:c.896_898delAGA (NP_000009.1:p.Lys299del) [GRCH38: NC_000017.11:g.7222684_7222686delAGA] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 8554073. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3 (less)
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Pathogenic
(Aug 19, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000321373.6
First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016 |
Comment:
Reported previously in association with VLCAD deficiency in multiple individuals (Souri et al., 1996; Schiff et al., 2013; Merinero et al., 2017); Functional studies in … (more)
Reported previously in association with VLCAD deficiency in multiple individuals (Souri et al., 1996; Schiff et al., 2013; Merinero et al., 2017); Functional studies in CHO cells found that the resultant mRNA and protein were unstable, that the resultant protein appeared abnormal in dimer assembly, and was associated with undetectable activity of the VLCAD enzyme (Souri et al., 1996); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 8554073, 23480858, 28755359, 27535533, 33278787, 32710939) (less)
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Likely pathogenic
(Sep 10, 2014)
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criteria provided, single submitter
Method: literature only
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Very long chain acyl-CoA dehydrogenase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220685.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Mar 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV003799675.3
First in ClinVar: Feb 13, 2023 Last updated: Jun 10, 2023 |
Comment:
The ACADVL c.896_898delAGA; p.Lys299del variant (rs398123094) has been described in individuals identified by newborn screening and in an individual described as having very long-chain acyl-CoA … (more)
The ACADVL c.896_898delAGA; p.Lys299del variant (rs398123094) has been described in individuals identified by newborn screening and in an individual described as having very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (Lin 2020, Schiff 2013, Souri 1996). This variant is also reported in ClinVar (Variation ID: 92292). It is found in the general population with an overall allele frequency of 0.002% (7/ 281832 alleles) in the Genome Aggregation Database. This variant deletes a single lysine residue leaving the rest of the protein in-frame. The lysine at codon 299 is conserved across mammals and the loss of this codon has been shown to result in an unstable transcript (Souri 1996). Based on available information, this variant is considered to be pathogenic. References: Lin Y et al. Newborn screening and genetic characteristics of patients with short- and very long-chain acyl-CoA dehydrogenase deficiencies. Clin Chim Acta. 2020 Nov;510:285-290. PMID: 32710939. Schiff M et al. Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab. 2013 May;109(1):21-7. PMID: 23480858. Souri M et al. Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients. Am J Hum Genet. 1996 Jan;58(1):97-106. PMID: 8554073. (less)
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Pathogenic
(Jan 01, 1996)
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no assertion criteria provided
Method: literature only
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VLCAD DEFICIENCY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000021850.2
First in ClinVar: Apr 04, 2013 Last updated: Mar 31, 2016 |
Comment on evidence:
In an infant with VLCAD deficiency (201475), Souri et al. (1996) found deletion of nucleotides 895-897 in the ACADVL gene, resulting in deletion of lys299 … (more)
In an infant with VLCAD deficiency (201475), Souri et al. (1996) found deletion of nucleotides 895-897 in the ACADVL gene, resulting in deletion of lys299 (K299X). (less)
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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 |
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High genetic burden in 163 Chinese children with status epilepticus. | Wang T | Seizure | 2021 | PMID: 33278787 |
Newborn screening and genetic characteristics of patients with short- and very long-chain acyl-CoA dehydrogenase deficiencies. | Lin Y | Clinica chimica acta; international journal of clinical chemistry | 2020 | PMID: 32710939 |
Novel missense mutations in the first Chinese patient with very-long-chain acyl-CoA dehydrogenase deficiency. | Law LK | Clinica chimica acta; international journal of clinical chemistry | 2007 | PMID: 16982043 |
Clinical and molecular heterogeneity in very-long-chain acyl-coenzyme A dehydrogenase deficiency. | Pons R | Pediatric neurology | 2000 | PMID: 10738914 |
Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. | Mathur A | Circulation | 1999 | PMID: 10077518 |
Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. | Andresen BS | American journal of human genetics | 1999 | PMID: 9973285 |
Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients. | Souri M | American journal of human genetics | 1996 | PMID: 8554073 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADVL | - | - | - | - |
Text-mined citations for rs387906252 ...
HelpRecord last updated Jul 29, 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.