Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000505787 | SCV000223977 | pathogenic | not provided | 2023-07-23 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate abnormal mRNA splicing (Kane et al., 2016); This variant is associated with the following publications: (PMID: 23222957, 27343256, 26482670, 34580403, 35700637, 36204321, 31184778, 33674710, 26917586, 36228046, 36410285) |
| Labcorp Genetics |
RCV000702544 | SCV000831402 | pathogenic | Vici syndrome | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 336 of the EPG5 protein (p.Gln336Arg). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs201757275, gnomAD 0.2%). This missense change has been observed in individuals with Vici syndrome (PMID: 26917586, 31184778; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 192333). 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. Studies have shown that this missense change results in partial intron inclusion and introduces a premature termination codon (PMID: 27343256). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| SIB Swiss Institute of Bioinformatics | RCV000702544 | SCV000899145 | likely pathogenic | Vici syndrome | 2019-01-17 | criteria provided, single submitter | curation | This variant is interpreted as a Likely pathogenic for Vici syndrome, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect (PMID:27343256). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. |
| New York Genome Center | RCV000702544 | SCV002099179 | likely pathogenic | Vici syndrome | 2021-03-27 | criteria provided, single submitter | clinical testing | |
| Pediatric Genetics Clinic, |
RCV000702544 | SCV001712174 | pathogenic | Vici syndrome | 2021-05-13 | no assertion criteria provided | clinical testing |