Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000813427 | SCV000953787 | uncertain significance | Congenital disorder of deglycosylation | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 550 of the NGLY1 protein (p.Tyr550Cys). This variant is present in population databases (rs373792768, gnomAD 0.004%). 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: 656905). 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 with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV002538161 | SCV003532595 | uncertain significance | Inborn genetic diseases | 2022-06-29 | criteria provided, single submitter | clinical testing | The c.1649A>G (p.Y550C) alteration is located in exon 11 (coding exon 11) of the NGLY1 gene. This alteration results from a A to G substitution at nucleotide position 1649, causing the tyrosine (Y) at amino acid position 550 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |