Submissions for variant NM_000018.4(ACADVL):c.623G>A (p.Gly208Glu)

dbSNP: rs2071251302

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV001200742	SCV001365037	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2019-11-01	criteria provided, single submitter	clinical testing	The NM_000018.3:c.623G>A (NP_000009.1:p.Gly208Glu) [GRCH38: NC_000017.11:g.7221952G>A] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant dose not meet any evidence codes reported in the ACMG guidelines.
PreventionGenetics, part of Exact Sciences	RCV003396814	SCV004119723	uncertain significance	ACADVL-related disorder	2022-11-10	criteria provided, single submitter	clinical testing	The ACADVL c.623G>A variant is predicted to result in the amino acid substitution p.Gly208Glu. This variant was reported along with a pathogenic ACADVL variant in an individual with newborn screen results suggestive of very long chain acyl-CoA dehydrogenase deficiency (VLCADD). VLCAD enzyme activity was reduced to 8% of control in lymphocytes from the described patient (Hesse et al. 2018. PubMed ID: 30194637). An alternate substitution impacting the same amino acid (p.Gly208Arg) was reported along with a missense variant of uncertain significance in a patient with newborn screen results suggestive of VLCADD (Pena et al. 2016. PubMed ID: 27209629). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect this variant could possibly be pathogenic, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.