Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000991823 | SCV001143596 | uncertain significance | not provided | 2024-10-23 | criteria provided, single submitter | clinical testing | Available data are insufficient to determine the clinical significance of the variant at this time. This variant has not been reported in large, multi-ethnic general populations. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual with clinical features associated with this gene. Polyphen and MutationTaster predict this amino acid change may be benign. |
| Revvity Omics, |
RCV000991823 | SCV003830779 | uncertain significance | not provided | 2019-05-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003769310 | SCV004587497 | uncertain significance | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-05-29 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 94 of the CLCN1 protein (p.Asp94Val). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. 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. This variant disrupts the p.Asp94 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31566103, 31567646). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CLCN1 protein function. ClinVar contains an entry for this variant (Variation ID: 804705). |