ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.1189T>C (p.Ter397Arg) (rs1555279757)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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 2020-07-15 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of mevalonate kinase deficiency (PMID: 27213830). This variant is also known as stop397R. ClinVar contains an entry for this variant (Variation ID: 546074). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

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