Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000665726 | SCV000789892 | likely pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2017-03-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000821368 | SCV000962123 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2018-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 346 of the GLB1 protein (p.Lys346Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with GM1-gangliosidosis (PMID: 16941474, 24777551, 19472408). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |