Submissions for variant NM_000431.4(MVK):c.545T>A (p.Leu182Ter)

dbSNP: rs1566147222

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000695407	SCV000823904	pathogenic	Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever	2018-04-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MVK are known to be pathogenic (PMID: 16835861, 17105862, 23834120). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with periodic fever and increased mevalonic acid (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu182*) in the MVK gene. It is expected to result in an absent or disrupted protein product.
PreventionGenetics, part of Exact Sciences	RCV004544947	SCV004800451	likely pathogenic	MVK-related disorder	2024-02-20	no assertion criteria provided	clinical testing	The MVK c.545T>A variant is predicted to result in premature protein termination (p.Leu182*). To our knowledge, this variant has not been reported in the literature or in the gnomAD database, indicating this variant is rare. Nonsense variants in MVK are expected to be pathogenic for autosomal recessive disease (see, Houten et al. 2000. PubMed ID: 11111075). This variant is interpreted as likely pathogenic.