Submissions for variant NM_000018.4(ACADVL):c.1838_1839delinsAA (p.Arg613Gln)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003499620	SCV004282299	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 613 of the ACADVL protein (p.Arg613Gln). This variant is present in population databases (no rsID available, gnomAD 0.0007%). This missense change has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 30194637, 32710939, 35281659). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg613 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17999356, 18670371, 23430950, 26881790, 28755359). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003499620	SCV005077403	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2024-04-05	criteria provided, single submitter	clinical testing	Variant summary: ACADVL c.1838_1839delinsAA (p.Arg613Gln) results in a conservative amino acid change located in the ACAD9/ACADV-like, C-terminal domain (IPR049448) of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.1e-06 in 282484 control chromosomes (gnomAD). Other variants affecting this residue have been determined to be pathogenic, including one that results in the same amino acid change. ClinVar contains an entry for this variant (Variation ID: 2725474). Based on the evidence outlined above, the variant was classified as pathogenic.