Total submissions: 11
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000383480 | SCV000341303 | uncertain significance | not provided | 2016-04-22 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
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, |
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, |
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 |
| Genome- |
RCV000264459 | SCV001737229 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2021-05-18 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000383480 | SCV001747793 | uncertain significance | not provided | 2021-04-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000383480 | SCV001785673 | uncertain significance | not provided | 2021-12-13 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified in the presence of a second ACADVL variant, phase unknown, in a patient with limb-girdle muscular dystrophy and histopathological dystrophic features, but no other phenotypic, metabolic, or familial information is available (Savarese et al., 2014); This variant is associated with the following publications: (PMID: 25214167) |
| Fulgent Genetics, |
RCV000264459 | SCV002809380 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-02-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000264459 | SCV003017801 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 585 of the ACADVL protein (p.Ala585Val). This variant is present in population databases (rs374729641, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of ACADVL-related conditions (PMID: 25214167). ClinVar contains an entry for this variant (Variation ID: 287514). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002518985 | SCV003689888 | uncertain significance | Inborn genetic diseases | 2022-01-25 | criteria provided, single submitter | clinical testing | The c.1754C>T (p.A585V) alteration is located in exon 19 (coding exon 19) of the ACADVL gene. This alteration results from a C to T substitution at nucleotide position 1754, causing the alanine (A) at amino acid position 585 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV000264459 | SCV001459265 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |