Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779090 | SCV000915576 | uncertain significance | MVK-related disorder | 2017-10-05 | criteria provided, single submitter | clinical testing | The MVK c.277_283delGAGGTTG (p.Glu93GlnfsTer38) variant results in a frameshift and is predicted to result in premature termination of the protein. The variant has been reported in a single study in which it is found in a single patient with mevalonate kinase deficiency in a compound heterozygous state (Mandey et al. 2006). Control data are unavailable for the p.Glu93GlnfsTer38 variant which not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium or the Genome Aggregation Database. Based on the limited evidence and the potential impact of frameshift variants, the p.Glu93GlnfsTer38 variant is classified as a variant of unknown significance but suspicious for pathogenicity for MVK-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV002514464 | SCV003441077 | pathogenic | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu93Glnfs*38) in the MVK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MVK are known to be pathogenic (PMID: 16835861, 17105862, 23834120). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mevalonate kinase deficiency (PMID: 16835861). ClinVar contains an entry for this variant (Variation ID: 97579). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV003137624 | SCV003822809 | pathogenic | not provided | 2022-06-30 | criteria provided, single submitter | clinical testing | |
| Unité médicale des maladies autoinflammatoires, |
RCV000083831 | SCV000115933 | not provided | Hyperimmunoglobulin D with periodic fever | no assertion provided | not provided |