Submissions for variant NM_000414.4(HSD17B4):c.1168G>T (p.Gly390Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003026003	SCV003322616	pathogenic	Bifunctional peroxisomal enzyme deficiency; Perrault syndrome	2022-02-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with HSD17B4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly390*) in the HSD17B4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HSD17B4 are known to be pathogenic (PMID: 11810648, 16385454).
Neuberg Centre For Genomic Medicine, NCGM	RCV003340590	SCV004047229	likely pathogenic	Bifunctional peroxisomal enzyme deficiency		criteria provided, single submitter	clinical testing	The stop gained variant c.1168G>T (p.Gly390Ter) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1168G>T variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely pathogenic.