Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000005417 | SCV003443329 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 128 of the SGSH protein (p.Pro128Leu). This variant is present in population databases (rs104894642, gnomAD 0.003%). This missense change has been observed in individual(s) with mucopolysaccharidosis type IIIA (PMID: 9554748, 12702166). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 5110). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SGSH protein function. Experimental studies have shown that this missense change affects SGSH function (PMID: 10727844). 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. |
| Baylor Genetics | RCV000005417 | SCV004201114 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-07-11 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000005417 | SCV000025599 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2003-04-01 | no assertion criteria provided | literature only |