Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521337 | SCV000619509 | likely pathogenic | not provided | 2017-08-03 | criteria provided, single submitter | clinical testing | The R106P (c.317 G>C) variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R106P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A different missense variant in the same residue (R106H) has previously been reported in association with mucopolysaccharidosis VI (Karageorgos et al., 2007), supporting the functional importance of this region of the protein. Additionally, several in-silico splice prediction models predict that the c.317 G>C variant, responsible for R106P, creates a cryptic acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |