Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669280 | SCV000794019 | uncertain significance | Mucopolysaccharidosis, MPS-III-C | 2017-09-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001390807 | SCV001592655 | pathogenic | Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 | 2023-09-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects HGSNAT function (PMID: 19823584, 20583299). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 553763). This missense change has been observed in individual(s) with Sanfilippo syndrome (PMID: 19479962, 31228227). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 489 of the HGSNAT protein (p.Ala489Glu). |