Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000578540 | SCV000680959 | pathogenic | not provided | 2022-10-14 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 32071843, 34939090, 32395402, 26795593, 31497478, 28330790) |
Ambry Genetics | RCV000622683 | SCV000740788 | pathogenic | Inborn genetic diseases | 2021-11-24 | criteria provided, single submitter | clinical testing | The c.1405C>T (p.R469*) alteration, located in exon 9 (coding exon 9) of the NGLY1 gene, consists of a C to T substitution at nucleotide position 1405. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 469. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of <0.01% (5/251086) total alleles studied. The highest observed frequency was 0.02% (3/18388) of East Asian alleles. This alteration has been identified as homozygous in multiple unrelated individuals with NGLY1-related congenital disorder of deglycosylation (Helbig, 2016; Chang, 2019). Based on the available evidence, this alteration is classified as pathogenic. |
Invitae | RCV000651488 | SCV000773340 | pathogenic | Congenital disorder of deglycosylation | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg469*) 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 (rs768131676, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with epilepsy and autism spectrum disorder (PMID: 26795593, 28330790). ClinVar contains an entry for this variant (Variation ID: 488990). 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. |