ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.3265C>A (p.Pro1089Thr)

dbSNP: rs147356378
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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.
GeneDx 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 (formerly Invitae), Labcorp RCV001089374 SCV001020280 likely benign Dilated cardiomyopathy 1DD 2025-01-19 criteria provided, single submitter clinical testing

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