Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_001270448.2:c.769_770insT

CA1139533037

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: acea36bd-bea8-4de2-bb8e-5d24a11d7d93

HGVS expressions

NM_001270448.2:c.769_770insT
NC_000017.11:g.7222785_7222786insT
CM000679.2:g.7222785_7222786insT
NC_000017.10:g.7126104_7126105insT
CM000679.1:g.7126104_7126105insT
NC_000017.9:g.7066828_7066829insT
NG_007975.1:g.7952_7953insT
NG_008391.2:g.2265_2266insA
ENST00000356839.10:c.997_998insT
ENST00000322910.9:c.*952_*953insT
ENST00000350303.9:c.931_932insT
ENST00000356839.9:c.997_998insT
ENST00000543245.6:c.1066_1067insT
ENST00000578824.5:n.146_147insT
ENST00000581378.5:n.715_716insT
ENST00000582379.1:n.381_382insT
ENST00000583858.5:n.26_27insT
NM_000018.3:c.997_998insT
NM_001033859.2:c.931_932insT
NM_001270447.1:c.1066_1067insT
NM_001270448.1:c.769_770insT
NM_000018.4:c.997_998insT
NM_001033859.3:c.931_932insT
NM_001270447.2:c.1066_1067insT

Pathogenic

Met criteria codes 3
PP4_Moderate PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.997_998insT (p.Ala333ValfsTer26) (NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 10/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). At least one patient with this variant displayed ꞵ-Oxidation Flux <20% of normal, which is highly specific for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (PP4_moderate, PMID:17999356). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PP4_moderate, PM2_supporting (ACADVL VCEP specifications version 1; approved November 8, 2021)
Met criteria codes
PP4_Moderate
At least one patient with this variant displayed ꞵ-Oxidation Flux <20% of normal, which is highly specific for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (PP4_moderate, PMID:17999356).
PVS1
The c.997_998insT (p.Ala333ValfsTer26) (NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 10/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
Approved on: 2023-03-28
Published on: 2023-03-28
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