Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000198315 | SCV000252532 | likely pathogenic | not provided | 2016-09-28 | criteria provided, single submitter | clinical testing | The p.Gly562Arg (GGC>CGC): c.1684 G>C in exon 8 of the WFS1 gene (NM_006005.3) G562R has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The G562R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G562R 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 that is conserved across species and most in silico analysis predict this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (L557F, R558H) have been reported as pathogenic supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
| Clinical Genomics, |
RCV003126589 | SCV003801418 | likely risk allele | Wolfram syndrome 1 | criteria provided, single submitter | research | Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs753237278 in Wolfram's syndrome yet. |