Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001897360 | SCV002157320 | uncertain significance | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2021-03-26 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CLCN1 protein function. This variant has not been reported in the literature in individuals with CLCN1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces leucine with isoleucine at codon 697 of the CLCN1 protein (p.Leu697Ile). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and isoleucine. |