Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003472709 | SCV004201085 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2024-01-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003472709 | SCV004457594 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-04-17 | criteria provided, single submitter | clinical testing | This variant disrupts a region of the SGSH protein in which other variant(s) (p.Trp479*) have been determined to be pathogenic (PMID: 21204211). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change affects a donor splice site in intron 7 of the SGSH gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with mucopolysaccharidosis type III (PMID: 21671382). 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. For these reasons, this variant has been classified as Pathogenic. |