Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001205333 | SCV001376583 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-06-20 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 6 of the SGSH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SGSH are known to be pathogenic (PMID: 11182930, 21204211, 22976768). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with mucopolysaccharidosis type IIIA (Invitae). ClinVar contains an entry for this variant (Variation ID: 936519). 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. |
| Illumina Laboratory Services, |
RCV001205333 | SCV004101370 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-06-22 | criteria provided, single submitter | clinical testing | The SGSH c.745+1G>C variant results in a substitution at the consensus splice donor site which may result in splicing defects. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database and was identified in a homozygous state. Based on the available evidence, the c.745+1G>C variant is classified as pathogenic for mucopolysaccharidosis type IIIA. |
| Baylor Genetics | RCV001205333 | SCV004201127 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-02-28 | criteria provided, single submitter | clinical testing |