Submissions for variant NM_005859.5(PURA):c.163C>T (p.Gln55Ter)

dbSNP: rs1085307472

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000489918	SCV000576516	pathogenic	not provided	2017-05-01	criteria provided, single submitter	clinical testing	The Q55X variant in the PURA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation. The Q55X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret Q55X as a pathogenic variant.
Invitae	RCV001205527	SCV001376789	pathogenic	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome	2023-08-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln55*) in the PURA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 268 amino acid(s) of the PURA protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PURA-related conditions. ClinVar contains an entry for this variant (Variation ID: 426145). This variant disrupts a region of the PURA protein in which other variant(s) (p.Tyr261*, p.Gln186*) have been determined to be pathogenic (PMID: 25439098). 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.