Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000677549 | SCV000803062 | uncertain significance | Mucopolysaccharidosis type 6 | 2018-01-01 | criteria provided, single submitter | curation | Very low frequency in ExAC (PM2) |
Illumina Laboratory Services, |
RCV000677549 | SCV000915137 | uncertain significance | Mucopolysaccharidosis type 6 | 2018-10-25 | criteria provided, single submitter | clinical testing | The ARSB c.347C>A (p.Pro116His) missense variant has been reported in a homozygous state in one patient with a severe clinical presentation of mucopolysaccharidosis, type VI (Villani et al. 1999). The p.Pro116His variant is reported at a frequency of 0.000009 in the European (non-Finnish) population of the Genome Aggregation Database but is based on one allele in a region of good sequencing coverage and is therefore presumed rare. Structural modelling of MPS-VI variants suggest that the majority of the variants destabilize the protein. Variants in which a proline is replaced by another amino acid, for example, the p.Pro116His variant, are likely to not be able to sustain a tight turn in the polypeptide chain (Litjens et al. 2001). The evidence for this variant is limited. The p.Pro116His variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for mucopolysaccharidosis, type VI. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |