ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1153C>T (p.Arg385Trp) (rs745832866)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000173952 SCV000225144 uncertain significance not provided 2015-04-23 criteria provided, single submitter clinical testing
Counsyl RCV000668844 SCV000793516 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2017-08-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000668844 SCV000915778 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2018-11-20 criteria provided, single submitter clinical testing The ACADVL c.1156C>T (p.Arg385Trp) is a missense variant that has been reported in at least five studies and found in at least five individuals with VLCAD deficiency, including a sibling pair, in a compound heterozygous state with a unique missense variant in each case (Boneh et al. 2006; Wasibren et al. 2013; Yamamoto et al. 2015; Evans et al. 2016; Merinero et al. 2017). This variant was inherited from the unaffected mother in a heterozygous state (Merinero et al. 2017) and is reported at a frequency of 0.000208 in the Latino population of the Genome Aggregation Database. Based on the collective evidence, the p.Arg386Cys variant is classified as likely pathogenic for VLCAD deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000668844 SCV001156591 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-06-06 criteria provided, single submitter clinical testing The ACADVL c.1153C>T; p.Arg385Trp variant (rs745832866), also reported as Arg345Trp, has been described in multiple individuals in association with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD; Boneh 2006, Merinero 2018, Ohashi 2004, Yamamoto 2015). It contains an entry in ClinVar (Variation ID: 193786), and is observed at a low overall frequency of 0.004% (10/251484 alleles) in the Genome Aggregation Database. The arginine at codon 385 is moderately conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. Additionally, recombinant ACADVL protein harboring the p.Arg385Trp substitution showed a reduction in enzyme activity comparted to wildtype (Ohashi 2004). Based on available information, this variant is considered likely pathogenic. REFERENCES Boneh et al. VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis. Mol. Genet. Metab. 2006; 88(2): 166-170. Merinero B et al. Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers. JIMD Rep. 2018;39:63-74. Ohashi et al. A new diagnostic test for VLCAD deficiency using immunohistochemistry. Neurology. 2004; 62(12): 2209-2213. Yamamoto H et al. Successful management of pregnancy with very-long-chain acyl-coenzyme A dehydrogenase deficiency. J Obstet Gynaecol Res. 2015 Jul;41(7):1126-8.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000668844 SCV001364916 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1153C>T (NP_000009.1:p.Arg385Trp) [GRCH38: NC_000017.11:g.7223208C>T] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 15210884. This variant meets the following evidence codes reported in the ACMG guidelines: PS1, PS3

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