ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.347C>A (p.Pro116His) (rs775780931)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000677549 SCV000803062 uncertain significance Mucopolysaccharidosis type VI 2018-01-01 criteria provided, single submitter curation Very low frequency in ExAC (PM2)
Illumina Clinical Services Laboratory,Illumina RCV000677549 SCV000915137 uncertain significance Mucopolysaccharidosis type VI 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.

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