Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001302836 | SCV001492060 | uncertain significance | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 73 of the GLB1 protein (p.Lys73Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs776889510, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with GLB1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| 3billion | RCV001810021 | SCV002058831 | uncertain significance | GM1 gangliosidosis type 3 | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). A different missense change at the same codon has been reported to be associated with GLB1 related disorder (PMID:15986423, PM5_P). A missense variant is a common mechanism associated with GM1-gangliosidosis (PP2_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |