Table 1.
A summary of the most common Rbm20 mutations.
| Nucleotide Change | Protein Change | Origin | Disease association | Exon | Domain | Reference |
|---|---|---|---|---|---|---|
| c.1901 G > A | R634Q | Both | Causative | 9 | RS | Brauch et al., 2009; Li et al., 2010 |
| c.1906 C > A | R636S | Familial | Causative | 9 | RS | Brauch et al., 2009 |
| c.1907 G > A | R636H | Familial | Causative | 9 | RS | Brauch et al., 2009; Li et al., 2010; Wells et al., 2013 |
| c.1909 A > G | S637G | Familial | Causative | 9 | RS | Brauch et al., 2009; Millat et al., 2011 |
| c.1913 C > T | P638L | Familial | Causative | 9 | RS | Brauch et al., 2009; Refaat et al., 2012; Long et al., 2017; Klauke et al., 2017 |
| c.247 C > A | L83I | Unknown | Possibly damaging by PolyPhen-2 predictions Tolerated protein function by SIFT predictions | 2 | Proline - rich region | Refaat et al., 2012 |
| c.1364 C > T | S455L | Unknown | Benign by PolyPhen-2 predictions Tolerated protein function by SIFT predictions | 4 | - | Refaat et al., 2012 |
| c.2109 G > C | R703S | Unknown | Probably damaging by PolyPhen-2 predictions Tolerated protein function by SIFT predictions | 9 | Downstream RS | Refaat et al., 2012 |
| c.2662 G > A | D888N | Unknown | Probably damaging by PolyPhen-2 predictions Tolerated protein function by SIFT predictions | 11 | Glutamate - rich region | Refaat et al., 2012 |
| c.3091 G > T | G1031∗ | Unknown | Likely deleterious as it leads to premature stop codon | 11 | – | Refaat et al., 2012 |
| c.3242 C > G | P1081R | Unknown | Probably damaging by PolyPhen-2 predictions Alter protein function by SIFT predictions | 11 | – | Refaat et al., 2012 |
| c.3616 G > A | E1206K | Unknown | Possibly damaging by PolyPhen-2 predictions Alter protein function by SIFT predictions | 14 | – | Refaat et al., 2012 |
| c.1661 G > A | V535I | Sporadic | No effect on Rbm20 function in splice reporter assay of titin exons | 6 | RRM | Li et al., 2010; Guo et al., 2012 |
| c.1958 C > T | R634W | Familial | Unknown | 9 | RS | Li et al., 2010 |
| c.1964 C > T | R636C | Familial | Causative | 9 | RS | Li et al., 2010; Rampersaud et al., 2011 |
| c.2205 G > A | R716Q | Familial | Causative | 9 | 60 residues downstream RS | Li et al., 2010 |
| c.1903 T > G | S635A | sporadic | Loss of function of Rbm20 function in splice reporter assay of titin exons | 9 | RS | Guo et al., 2012 |
| c.2062 C > T | R688∗ | Familial | Likely Pathogenic (class 4) rare (minor allele frequency ≤ 0.1%) nonsense variant | 9 | downstream RS | Waldmüller et al., 2015 |
| c.3545 G > A | R1182H | Unknown | Benign by PolyPhen-2 predictions Alter protein function by SIFT predictions Disease causing by mutation Taster predictions | 13 | ZnF | Zhao et al., 2015 |
| c.2737 G > A | E913K | Familial | Causative | 11 | Glutamate - rich region | Beqqali et al., 2016 |
| c.1904 C > G | S635C | Familial | Likely Pathogenic (Class 4) based on ACMG classification | 9 | RS | Klauke et al., 2017 |
All mutations are missense except for two nonsense mutations (marked with∗). Most mutations occur in a 5-amino acid hotspot comprised of the residues 634, 635, 636, 637, and 638 in the RS domain of the protein. The RBM20 nucleotide position is based on the NCBI reference sequence NM_001134363.1 and amino acid positions are based on the NCBI reference sequence NP_001127835.1. RS, Arginine-Serine rich; RRM, RNA-recognition-motif, ZnF, Zinc Finger; ACMG, American College of Medical Genetics and Genomics.