Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000658189 | SCV000779960 | uncertain significance | not provided | 2018-05-09 | criteria provided, single submitter | clinical testing | The Q204H variant in the KRT1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q204H variant is not observed in large population cohorts, indicating it is not a common polymorphisms (Lek et al., 2016). The Q204H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Nevertheless, while Q204H is located in the conserved 1A region of the alpha-helical rod domain, it lies outside the mutational hotspot at the helix initiation motif. Therefore, we interpret Q204H as a variant of uncertain significance. |