Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000550715 | SCV000636308 | uncertain significance | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2019-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 663 of the CLCN1 protein (p.Arg663His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. The frequency data for this variant in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a CLCN1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |