Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000542289 | SCV000654098 | uncertain significance | Congenital disorder of deglycosylation | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 239 of the NGLY1 protein (p.Glu239Asp). This variant is present in population databases (rs754083716, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NGLY1-related conditions. ClinVar contains an entry for this variant (Variation ID: 474232). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NGLY1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001556237 | SCV001777780 | uncertain significance | not provided | 2019-07-02 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
New York Genome Center | RCV000542289 | SCV002025643 | uncertain significance | Congenital disorder of deglycosylation | 2020-04-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002530238 | SCV003564639 | uncertain significance | Inborn genetic diseases | 2021-04-03 | criteria provided, single submitter | clinical testing | The c.717A>C (p.E239D) alteration is located in exon 5 (coding exon 5) of the NGLY1 gene. This alteration results from a A to C substitution at nucleotide position 717, causing the glutamic acid (E) at amino acid position 239 to be replaced by an aspartic acid (D). The p.E239D alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |