ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.1024C>A (p.Pro342Thr)

gnomAD frequency: 0.00007  dbSNP: rs876657971
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Total submissions: 5
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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 RCV000215489 SCV000272348 benign not specified 2019-12-11 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000766615 SCV000576797 uncertain significance not provided 2018-03-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RBM20 gene. The P342T variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P342T 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 where threonine is present as the wild type in several species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV000810104 SCV000950293 benign Dilated cardiomyopathy 1DD 2023-05-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002381746 SCV002691559 uncertain significance Cardiovascular phenotype 2022-09-15 criteria provided, single submitter clinical testing The p.P342T variant (also known as c.1024C>A), located in coding exon 2 of the RBM20 gene, results from a C to A substitution at nucleotide position 1024. The proline at codon 342 is replaced by threonine, an amino acid with highly similar properties. This alteration has been reported in an adolescent female with acute heart failure who also had variants in TTN (reported as p.Arg23388Ter) and DMD (reported as p.Val218Ile) (Brown EE et al. Cardiol Young, 2019 Jul;29:917-921).This amino acid position is not well conserved in available 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000810104 SCV003920385 uncertain significance Dilated cardiomyopathy 1DD 2021-03-30 criteria provided, single submitter clinical testing RBM20 NM_001134363.2 exon 2 p.Pro342Thr (c.1024C>A): This variant has not been reported in the literature and is present in 0.03% (5/16630) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/10-112541391-C-A). This variant is present in ClinVar (Variation ID:229182). This variant amino acid Threonine (Thr) is present in several species including the alpaca, bactrian camel, and shrew, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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