Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000810175 | SCV000950366 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2022-11-02 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 654251). This variant has been observed in individual(s) with GM1 gangliosidosis type II (PMID: 25936995). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change affects codon 493 of the GLB1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GLB1 protein. This variant also falls at the last nucleotide of exon 14, which is part of the consensus splice site for this exon. |
Genome |
RCV000810175 | SCV001338918 | not provided | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 12-19-2018 by Lab or GTR ID 500031. GenomeConnect-GM1 assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. |