Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000479255 | SCV000574395 | uncertain significance | not provided | 2017-03-29 | criteria provided, single submitter | clinical testing | The R2166Q variant has not been published as pathogenic or been reported as benign to our knowledge. The R2166Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R2166Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Though this substitution occurs at a position that is conserved in most mammals, Q2166 is wild-type for at least one mammalian and one non-mammalian species. Furthermore, the majority of in silico analyses predict this variant likely does not alter the protein structure/function. |
Invitae | RCV000796935 | SCV000936470 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-03-20 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV003532144 | SCV004363470 | uncertain significance | Cardiomyopathy | 2023-02-22 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 2166 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden unexplained death and suspected of having dilated cardiomyopathy (PMID: 27930701). This variant has been identified in 2/251436 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |