Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000252744 | SCV000319678 | uncertain significance | Cardiovascular phenotype | 2015-05-18 | criteria provided, single submitter | clinical testing | The p.I252V variant (also known as c.754A>G), located in coding exon 6 of the DSC2 gene, results from an A to G substitution at nucleotide position 754. The isoleucine at codon 252 is replaced by valine, an amino acid with highly similar properties. Based on data from ExAC, the G allele was reported in 1 of 120,580 total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed May 15, 2015]). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6,503 samples (13,006 alleles) with coverage at this position. This amino acid position is not conserved in available vertebrate species, and valine is the reference amino acid in many 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 variant remains unclear. |
Invitae | RCV000644639 | SCV000766342 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-06-19 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 264041). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs751996698, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 252 of the DSC2 protein (p.Ile252Val). |
Color Diagnostics, |
RCV001181618 | SCV001346800 | likely benign | Cardiomyopathy | 2019-04-01 | criteria provided, single submitter | clinical testing |