Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485201 | SCV000565031 | likely pathogenic | not provided | 2016-09-20 | criteria provided, single submitter | clinical testing | The K291E variant that is likely pathogenic has been reported previously in one family with maturity onset of diabetes of the young (MODY) (Osbak et al., 2009). The K291E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). K291E 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 within the hexokinase domain that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants at the same (K291T) and in nearby residues (Q287K/L, Y289H/N/C, E290D, L292P, I293T, G294D, G295C/R/S/D) have been reported in the Human Gene Mutation Database in association with MODY (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |