ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1754C>T (p.Ala585Val) (rs374729641)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000383480 SCV000341303 uncertain significance not provided 2016-04-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000264459 SCV000406329 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000264459 SCV001157896 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-06-06 criteria provided, single submitter clinical testing The ACADVL c.1754C>T; p.Ala585Val variant (rs374729641) is reported in the literature in at least one individual affected with a nonsyndromic muscle disorder, who carried a second pathogenic ACADVL variant (Savarese 2014). This variant is reported in ClinVar (Variation ID: 287514), and is found in the general population with an overall allele frequency of 0.009% (25/282600 alleles) in the Genome Aggregation Database. The alanine at codon 585 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Ala585Val variant is uncertain at this time. References: Savarese M et al. MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples. Acta Neuropathol Commun. 2014 Sep 11;2:100.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000264459 SCV001365214 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1754C>T (NP_000009.1:p.Ala585Val) [GRCH38: NC_000017.11:g.7224811C>T] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PP3

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