Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000657855 | SCV000779613 | likely pathogenic | not provided | 2018-05-21 | criteria provided, single submitter | clinical testing | The c.1189 T>C variant has been reported previously as compound heterozygous with a pathogenic variant in association with MKD deficiency; however, this patient excreted normal levels of melvalonic acid (Ter Haar et al., 2016). It causes a stop loss and protein extension, and creates a new Stop codon at position 34 of the new reading frame, denoted p.Ter397ArgextX34. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be likely pathogenic. |
| Invitae | RCV001297383 | SCV001486395 | uncertain significance | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2022-06-13 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 546074). This variant is also known as stop397R. This frameshift has been observed in individual(s) with clinical features of mevalonate kinase deficiency (PMID: 27213830). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the MVK gene (p.*397Argext*34). While this is not anticipated to result in nonsense mediated decay, it is expected to extend the MVK protein by an additional 34 amino acids. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. |