NM_000018.4(ACADVL):c.1024T>C (p.Phe342Leu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 2023
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:: RCV003489845.1

Allele description [Variation Report for NM_000018.4(ACADVL):c.1024T>C (p.Phe342Leu)]

NM_000018.4(ACADVL):c.1024T>C (p.Phe342Leu)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.1024T>C (p.Phe342Leu)

HGVS:

NC_000017.11:g.7222812T>C
NG_007975.1:g.7979T>C
NG_008391.2:g.2239A>G
NM_000018.4:c.1024T>CMANE SELECT
NM_001033859.3:c.958T>C
NM_001270447.2:c.1093T>C
NM_001270448.2:c.796T>C
NP_000009.1:p.Phe342Leu
NP_001029031.1:p.Phe320Leu
NP_001257376.1:p.Phe365Leu
NP_001257377.1:p.Phe266Leu
NC_000017.10:g.7126131T>C
NM_000018.3:c.1024T>C

Protein change:

F266L

Links:

dbSNP: rs1356652354

NCBI 1000 Genomes Browser:

rs1356652354

Molecular consequence:

NM_000018.4:c.1024T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.958T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1093T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.796T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004241018	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26385305, 32778825, 24503138 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004241018

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 13, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

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, Burrage LC, Gibson JB, Strenk ME, Lose EJ, Bick DP, Elsea SH, Sutton VR, Sun Q, Graham BH, Craigen WJ, Zhang VW, Wong LJ.

Mol Genet Metab. 2015 Nov;116(3):139-45. doi: 10.1016/j.ymgme.2015.08.011. Epub 2015 Sep 2.

PubMed [citation]

PMID:: 26385305
PMCID:: PMC4790081

The role of exome sequencing in newborn screening for inborn errors of metabolism.

Adhikari AN, Gallagher RC, Wang Y, Currier RJ, Amatuni G, Bassaganyas L, Chen F, Kundu K, Kvale M, Mooney SD, Nussbaum RL, Randi SS, Sanford J, Shieh JT, Srinivasan R, Sunderam U, Tang H, Vaka D, Zou Y, Koenig BA, Kwok PY, Risch N, et al.

Nat Med. 2020 Sep;26(9):1392-1397. doi: 10.1038/s41591-020-0966-5. Epub 2020 Aug 10.

PubMed [citation]

PMID:: 32778825
PMCID:: PMC8800147

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004241018.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: ACADVL c.1024T>C (p.Phe342Leu) results in a non-conservative amino acid change located in the C-terminal domain (IPR009075) 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 251308 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1024T>C has been reported in the literature in individuals affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency (e.g., Merritt_2014, Miller_2015, Adhikari_2020). However, these reports do not provide unequivocal conclusions about association of the variant with Very Long Chain Acyl-CoA Dehydrogenase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32778825, 24503138, 26385305). Three submitters have reported 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 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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