Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001961412 | SCV002254779 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-09-18 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs767293228, ExAC 0.002%). This sequence change replaces glutamine with histidine at codon 72 of the DSC2 protein (p.Gln72His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. |
Ambry Genetics | RCV002425344 | SCV002729223 | uncertain significance | Cardiovascular phenotype | 2022-02-20 | criteria provided, single submitter | clinical testing | The p.Q72H variant (also known as c.216A>C), located in coding exon 3 of the DSC2 gene, results from an A to C substitution at nucleotide position 216. The glutamine at codon 72 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |