Submissions for variant NM_018297.4(NGLY1):c.622C>T (p.Gln208Ter)

dbSNP: rs200561967

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001007960	SCV001167686	pathogenic	not provided	2019-03-20	criteria provided, single submitter	clinical testing	The Q208X nonsense variant in the NGLY1 gene has been reported previously in two siblings with features of a NGLY1-related disorder who also had a second variant on the opposite allele (He et al., 2015). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret Q208X as a pathogenic variant.
Invitae	RCV000496134	SCV004293432	pathogenic	Congenital disorder of deglycosylation	2024-01-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln208*) in the NGLY1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NGLY1 are known to be pathogenic (PMID: 24651605). This variant is present in population databases (rs200561967, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of congenital disorder of glycosylation type 1V (PMID: 25900930). ClinVar contains an entry for this variant (Variation ID: 221578). For these reasons, this variant has been classified as Pathogenic.
Medical Biochemical Genetics, National Human Genome institute, NIH, National Institutes of Health	RCV000496134	SCV000259181	pathogenic	Congenital disorder of deglycosylation	2016-01-07	no assertion criteria provided	clinical testing
GeneReviews	RCV000496134	SCV000891723	not provided	Congenital disorder of deglycosylation		no assertion provided	literature only	Mild impairment