Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000114362 | SCV000245514 | pathogenic | Congenital disorder of deglycosylation | 2013-05-24 | criteria provided, single submitter | clinical testing | This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory homozygous in a 19-year-old female with static encephalopathy, peripheral neuropathy, dysphagia, intellectual disability, abnormal movements, abnormal tone, cortical visual impairment, osteoporosis, scoliosis. This patient has since been published (PMID: 24651605). |
| Gene |
RCV001008537 | SCV001168309 | pathogenic | not provided | 2019-03-20 | criteria provided, single submitter | clinical testing | The c.1370dupG pathogenic variant in the NGLY1 gene has been reported previously as a homozygous pathogenic variant in a patient with features of NGLY1 deficiency (Enns et al., 2014; Lam et al., 2017). The duplication causes a frameshift starting with codon Arginine 458, changes this amino acid to a Lysine residue and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Arg458LysfsX14. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1370dupG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1370dupG as a pathogenic variant. |
| Invitae | RCV000114362 | SCV004293431 | pathogenic | Congenital disorder of deglycosylation | 2023-12-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg458Lysfs*14) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with N-glycanase 1 deficiency (PMID: 24651605, 27388694). ClinVar contains an entry for this variant (Variation ID: 126422). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000114362 | SCV000147974 | pathogenic | Congenital disorder of deglycosylation | 2014-03-20 | no assertion criteria provided | literature only |