ClinVar Miner

Submissions for variant NM_018297.4(NGLY1):c.1231C>T (p.Arg411Ter)

gnomAD frequency: 0.00001  dbSNP: rs146140738
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802056 SCV000941869 pathogenic Congenital disorder of deglycosylation 2024-11-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg411*) 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 (rs146140738, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with NGLY1-related conditions (PMID: 31965062). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 647531). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001008026 SCV001167758 pathogenic not provided 2023-10-23 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31440721, 33497766, 31965062)
Ambry Genetics RCV002537141 SCV003670542 pathogenic Inborn genetic diseases 2022-12-21 criteria provided, single submitter clinical testing The c.1231C>T (p.R411*) alteration, located in exon 8 (coding exon 8) of the NGLY1 gene, consists of a C to T substitution at nucleotide position 1231. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 411. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration was detected in conjunction with another alteration in NGLY1, in multiple individuals with NGLY1-related congenital disorder of deglycosylation (Abuduxikuer, 2020). Based on the available evidence, this alteration is classified as pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV003338810 SCV004046951 pathogenic Congenital disorder of deglycosylation 1 criteria provided, single submitter clinical testing The stop gained variant c.1231C>T (p.Arg411Ter) in NGLY1 has been reported to the ClinVar database as Pathogenic. The p.Arg411Ter variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.002789% is reported in gnomAD. The nucleotide change in NGLY1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic .
Fulgent Genetics, Fulgent Genetics RCV003338810 SCV005658061 pathogenic Congenital disorder of deglycosylation 1 2024-03-21 criteria provided, single submitter clinical testing

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