Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000001290 | SCV000474016 | uncertain significance | Mucopolysaccharidosis, MPS-III-C | 2017-04-27 | criteria provided, single submitter | clinical testing | The HGSNAT c.1345dupG (p.Asp449GlyfsTer21) variant results in a frameshift and is expected to result in premature premature truncation of the protein. Fan et al. (2006) reported this variant in a compound heterozygous state with a splicing variant in one of two cell lines from individuals with mucopolysaccharidosis type III-C. The p.Asp449GlyfsTer21 variant is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium. This frequency is based on one allele in a region of good sequencing coverage, so the variant is presumed to be rare. Based on the limited evidence and the potential impact of frameshift variants, the p.Asp449GlyfsTer21 variant is classified as a variant of unknown significance but suspicious for pathogenicity for mucopolysaccharidosis type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Genomic Research Center, |
RCV000001290 | SCV000784408 | pathogenic | Mucopolysaccharidosis, MPS-III-C | 2018-03-05 | criteria provided, single submitter | clinical testing | |
Genomic Research Center, |
RCV000662072 | SCV000784409 | pathogenic | Retinitis pigmentosa 73 | 2018-03-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001390806 | SCV001592654 | pathogenic | Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 | 2023-12-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp449Glyfs*21) in the HGSNAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). This variant is present in population databases (rs483352894, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type IIIC (PMID: 16960811, 19479962, 31228227). 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: 1231). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000001290 | SCV000021440 | pathogenic | Mucopolysaccharidosis, MPS-III-C | 2006-10-01 | no assertion criteria provided | literature only |