Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000175599 | SCV000227114 | uncertain significance | not provided | 2014-06-24 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000672371 | SCV000797470 | likely pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2018-01-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000707313 | SCV000836403 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2019-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 49 of the GLB1 protein (p.Arg49Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs72555358, ExAC 0.009%). This variant has been observed in the homozygous state or in combination with other GLB1 variants in individuals with GM1-gangliosidosis (PMID: 15365997, 21520340, 26646981, 25936995, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 923). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg49 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been observed in individuals with GLB1-related conditions (PMID: 15986423, 30267299), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000000971 | SCV000021121 | pathogenic | Infantile GM1 gangliosidosis | 1991-09-01 | no assertion criteria provided | literature only |