ClinVar Genomic variation as it relates to human health
NM_000018.4(ACADVL):c.260T>C (p.Val87Ala)
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.260T>C (p.Val87Ala)
Variation ID: 203570 Accession: VCV000203570.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7220659 (GRCh38) [ NCBI UCSC ] 17: 7123978 (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 Jul 16, 2020 Feb 14, 2024 Sep 23, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000018.4:c.260T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000009.1:p.Val87Ala missense NM_001033859.3:c.194T>C NP_001029031.1:p.Val65Ala missense NM_001270447.2:c.329T>C NP_001257376.1:p.Val110Ala missense NM_001270448.2:c.32T>C NP_001257377.1:p.Val11Ala missense NC_000017.11:g.7220659T>C NC_000017.10:g.7123978T>C NG_007975.1:g.5826T>C NG_008391.2:g.4392A>G - Protein change
- V87A, V11A, V110A, V65A
- Other names
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- Canonical SPDI
- NC_000017.11:7220658:T:C
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
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
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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 |
1708 | 1913 |
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
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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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Uncertain significance (4) |
reviewed by expert panel
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Sep 23, 2022 | RCV001200682.6 |
Submissions - Germline
Classification
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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
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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
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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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Uncertain significance
(Sep 23, 2022)
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reviewed by expert panel
Method: curation
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Very long chain acyl-CoA dehydrogenase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen ACADVL Variant Curation Expert Panel, ClinGen
Accession: SCV002576745.2
First in ClinVar: Oct 08, 2022 Last updated: Apr 23, 2023 |
Comment:
The c.260T>C variant in ACADVL has been reported in one individual with very long chain acyl-CoA dehydrogenase deficiency in the literature with reduced VLCAD activity … (more)
The c.260T>C variant in ACADVL has been reported in one individual with very long chain acyl-CoA dehydrogenase deficiency in the literature with reduced VLCAD activity (PP4; PMID: 30194637). In this same proband, the variant was detected one time not confirmed in-trans with the pathogenic variant c.848T>C (PM3_supporting; PMID: 30194637). The highest population minor allele frequency in gnomAD is 0.000003977 in the Latino population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.76, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). In summary, this variant currently has uncertain pathogenic significance for very long chain acyl-CoA dehydrogenase deficiency in an autosomal recessive manner based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PP4; PM3_supporting; PM2_Supporting; PP3. (less)
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Likely 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: SCV001365003.2
First in ClinVar: Jul 16, 2020 Last updated: Jul 16, 2020 |
Comment:
The NM_000018.3:c.260T>C (NP_000009.1:p.Val87Ala) [GRCH38: NC_000017.11:g.7220659T>C] variant in ACADVL gene is interpretated to be Likely pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been … (more)
The NM_000018.3:c.260T>C (NP_000009.1:p.Val87Ala) [GRCH38: NC_000017.11:g.7220659T>C] variant in ACADVL gene is interpretated to be Likely pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PS3, PM3 PP3, PP4 (less)
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Likely pathogenic
(Aug 25, 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:
unknown
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Baylor Genetics
Accession: SCV004212682.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Dec 09, 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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Invitae
Accession: SCV003523703.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 87 of the ACADVL protein (p.Val87Ala). … (more)
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 87 of the ACADVL protein (p.Val87Ala). This variant is present in population databases (rs796051907, gnomAD 0.003%). This missense change has been observed in individual(s) with very long chain acyl-coA dehydrogenase deficiency (PMID: 30194637). ClinVar contains an entry for this variant (Variation ID: 203570). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADVL protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (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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The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD). | Hesse J | Journal of inherited metabolic disease | 2018 | PMID: 30194637 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/be1f9e39-8225-4a2c-ab44-d75c12a1681d | - | - | - | - |
Text-mined citations for rs796051907 ...
HelpRecord last updated Feb 14, 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.