Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16694 | 50305;50306;50307 | chr2:178612445;178612444;178612443 | chr2:179477172;179477171;179477170 |
| N2AB | 15053 | 45382;45383;45384 | chr2:178612445;178612444;178612443 | chr2:179477172;179477171;179477170 |
| N2A | 14126 | 42601;42602;42603 | chr2:178612445;178612444;178612443 | chr2:179477172;179477171;179477170 |
| N2B | 7629 | 23110;23111;23112 | chr2:178612445;178612444;178612443 | chr2:179477172;179477171;179477170 |
| Novex-1 | 7754 | 23485;23486;23487 | chr2:178612445;178612444;178612443 | chr2:179477172;179477171;179477170 |
| Novex-2 | 7821 | 23686;23687;23688 | chr2:178612445;178612444;178612443 | chr2:179477172;179477171;179477170 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs779633258  |
0.01 | 0.543 | N | 0.311 | 0.159 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 6.51E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs779633258 |
0.01 | 0.543 | N | 0.311 | 0.159 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs779633258 |
0.01 | 0.543 | N | 0.311 | 0.159 | None | gnomAD-4.0.0 | 6.58224E-06 | None | None | None | None | N | None | 2.41464E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9724 | likely_pathogenic | 0.9756 | pathogenic | -0.097 | Destabilizing | 0.992 | D | 0.442 | neutral | None | None | None | None | N |
| R/C | 0.9194 | likely_pathogenic | 0.9148 | pathogenic | -0.182 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| R/D | 0.9886 | likely_pathogenic | 0.9903 | pathogenic | -0.003 | Destabilizing | 0.999 | D | 0.5 | neutral | None | None | None | None | N |
| R/E | 0.9553 | likely_pathogenic | 0.9699 | pathogenic | 0.068 | Stabilizing | 0.992 | D | 0.401 | neutral | None | None | None | None | N |
| R/F | 0.9822 | likely_pathogenic | 0.9849 | pathogenic | -0.294 | Destabilizing | 1.0 | D | 0.572 | neutral | None | None | None | None | N |
| R/G | 0.9325 | likely_pathogenic | 0.933 | pathogenic | -0.31 | Destabilizing | 0.994 | D | 0.391 | neutral | N | 0.439072088 | None | None | N |
| R/H | 0.7089 | likely_pathogenic | 0.7052 | pathogenic | -0.813 | Destabilizing | 1.0 | D | 0.399 | neutral | None | None | None | None | N |
| R/I | 0.961 | likely_pathogenic | 0.9675 | pathogenic | 0.433 | Stabilizing | 1.0 | D | 0.585 | neutral | None | None | None | None | N |
| R/K | 0.4884 | ambiguous | 0.4446 | ambiguous | -0.121 | Destabilizing | 0.543 | D | 0.311 | neutral | N | 0.418811829 | None | None | N |
| R/L | 0.89 | likely_pathogenic | 0.9012 | pathogenic | 0.433 | Stabilizing | 0.996 | D | 0.391 | neutral | None | None | None | None | N |
| R/M | 0.9619 | likely_pathogenic | 0.9686 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.429 | neutral | N | 0.48150006 | None | None | N |
| R/N | 0.98 | likely_pathogenic | 0.9819 | pathogenic | 0.173 | Stabilizing | 0.999 | D | 0.359 | neutral | None | None | None | None | N |
| R/P | 0.984 | likely_pathogenic | 0.9846 | pathogenic | 0.277 | Stabilizing | 1.0 | D | 0.503 | neutral | None | None | None | None | N |
| R/Q | 0.6545 | likely_pathogenic | 0.6771 | pathogenic | 0.048 | Stabilizing | 0.998 | D | 0.36 | neutral | None | None | None | None | N |
| R/S | 0.9783 | likely_pathogenic | 0.9807 | pathogenic | -0.259 | Destabilizing | 0.989 | D | 0.417 | neutral | N | 0.392954371 | None | None | N |
| R/T | 0.9538 | likely_pathogenic | 0.9642 | pathogenic | -0.044 | Destabilizing | 0.998 | D | 0.388 | neutral | N | 0.454645444 | None | None | N |
| R/V | 0.9649 | likely_pathogenic | 0.9709 | pathogenic | 0.277 | Stabilizing | 0.999 | D | 0.585 | neutral | None | None | None | None | N |
| R/W | 0.8797 | likely_pathogenic | 0.8925 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.67 | neutral | N | 0.482547066 | None | None | N |
| R/Y | 0.9644 | likely_pathogenic | 0.9667 | pathogenic | 0.114 | Stabilizing | 1.0 | D | 0.499 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.