Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001377322 | SCV001574628 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2020-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 90 of the SGSH protein (p.Gly90Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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. A different variant (c.268G>A) giving rise to the same protein effect observed here (p.Gly90Arg) has been determined to be pathogenic (PMID: 21204211, 21455105, 24875751). This suggests that this variant is also likely to be causative of disease. 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 has not been reported in the literature in individuals with SGSH-related conditions. This variant is not present in population databases (ExAC no frequency). |