Submissions for variant NM_000431.4(MVK):c.943_944del (p.Leu315fs)

dbSNP: rs776735249

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001090937	SCV001246721	likely pathogenic	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002489730	SCV002795708	likely pathogenic	Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever	2024-03-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002489730	SCV004577611	pathogenic	Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever	2022-12-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu315Glyfs*51) in the MVK gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 82 amino acid(s) of the MVK protein. This variant is present in population databases (rs776735249, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with autosomal dominant porokeratosis (PMID: 33279647). This variant disrupts a region of the MVK protein in which other variant(s) (p.Arg388*) have been determined to be pathogenic (PMID: 23146290, 23998246, 27012807). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001797820	SCV002041491	pathogenic	Mevalonic aciduria		no assertion criteria provided	clinical testing