Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000151737 | SCV000200097 | likely benign | not specified | 2014-01-24 | criteria provided, single submitter | clinical testing | Pro1089Thr in exon 11 of RBM20: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, 5 mammals have a threonine (Thr) at this position despite high nearby amino acid conservation. In addition, computational analyses (AlignGVGD and PolyPhen2 ) do not suggest a high likelihood of impact to the protein. |
Gene |
RCV000766696 | SCV000236366 | uncertain significance | not provided | 2013-10-02 | criteria provided, single submitter | clinical testing | p.Pro1089Thr (CCC>ACC): c.3265 C>A in exon 11 of the RBM20 gene (NM_001134363.1). The Pro1089Thr variant in the RBM20 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Pro1089Thr was not observed in approximately 2000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although Pro1089Thr results in a non-conservative amino acid substitution of a non polar Proline with a polar Threonine, this substitution occurs at a position that is not well conserved across species. Consequently, in silico analysis predicts Pro1089Thr is benign to the protein structure/function. Only one mutation in a nearby residue (Pro1081Arg) has been reported in association with DCM (Refaat M et al., 2012). With the clinical and molecular information available at this time, we cannot definitively determine if Pro1089Thr is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s). |
Ambry Genetics | RCV000619097 | SCV000736291 | likely benign | Cardiovascular phenotype | 2016-08-25 | 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. |
Labcorp Genetics |
RCV001089374 | SCV001020280 | likely benign | Dilated cardiomyopathy 1DD | 2025-01-19 | criteria provided, single submitter | clinical testing |