Submissions for variant NM_005859.5(PURA):c.175C>T (p.Gln59Ter)

dbSNP: rs1561793115

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000707077	SCV000836157	pathogenic	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome	2023-05-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PURA protein in which other variant(s) (p.Gln163*, p.Tyr261*, p.Gln186*) have been determined to be pathogenic (PMID: 25439098; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 582890). This variant has not been reported in the literature in individuals affected with PURA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln59*) in the PURA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 264 amino acid(s) of the PURA protein.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003238197	SCV002009638	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing