Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413353 | SCV000491947 | uncertain significance | not specified | 2016-11-22 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the RBM20 gene. The G181R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 2,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G181R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, this variant is not located in the exon 9 hot-spot" region of the RBM20 gene, where many pathogenic variants are located (Brauch et al., 2010).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign." |
| Illumina Laboratory Services, |
RCV001105154 | SCV001262078 | uncertain significance | Dilated cardiomyopathy 1DD | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV001105154 | SCV001697638 | likely benign | Dilated cardiomyopathy 1DD | 2023-12-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002348132 | SCV002652848 | likely benign | Cardiovascular phenotype | 2020-01-02 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000413353 | SCV003934745 | likely benign | not specified | 2023-05-15 | criteria provided, single submitter | clinical testing |