Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34424 | 103495;103496;103497 | chr2:178533345;178533344;178533343 | chr2:179398072;179398071;179398070 |
| N2AB | 32783 | 98572;98573;98574 | chr2:178533345;178533344;178533343 | chr2:179398072;179398071;179398070 |
| N2A | 31856 | 95791;95792;95793 | chr2:178533345;178533344;178533343 | chr2:179398072;179398071;179398070 |
| N2B | 25359 | 76300;76301;76302 | chr2:178533345;178533344;178533343 | chr2:179398072;179398071;179398070 |
| Novex-1 | 25484 | 76675;76676;76677 | chr2:178533345;178533344;178533343 | chr2:179398072;179398071;179398070 |
| Novex-2 | 25551 | 76876;76877;76878 | chr2:178533345;178533344;178533343 | chr2:179398072;179398071;179398070 |
| 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/G | None | None | 1.0 | N | 0.631 | 0.459 | 0.37953744168 | gnomAD-4.0.0 | 1.59155E-06 | None | None | None | None | N | None | 5.65227E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs972117588  |
-0.005 | 1.0 | N | 0.674 | 0.506 | 0.501940320817 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/T | rs972117588 |
-0.005 | 1.0 | N | 0.674 | 0.506 | 0.501940320817 | gnomAD-4.0.0 | 2.05281E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99408E-07 | 0 | 3.3129E-05 |
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 | 0.783 | likely_pathogenic | 0.8191 | pathogenic | -0.798 | Destabilizing | 0.999 | D | 0.622 | neutral | None | None | None | None | N |
| R/C | 0.4169 | ambiguous | 0.4429 | ambiguous | -0.665 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/D | 0.9373 | likely_pathogenic | 0.9475 | pathogenic | -0.257 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/E | 0.685 | likely_pathogenic | 0.7226 | pathogenic | -0.154 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| R/F | 0.8795 | likely_pathogenic | 0.8899 | pathogenic | -0.783 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/G | 0.6643 | likely_pathogenic | 0.694 | pathogenic | -1.092 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.49306307 | None | None | N |
| R/H | 0.1935 | likely_benign | 0.2119 | benign | -1.416 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/I | 0.6905 | likely_pathogenic | 0.7138 | pathogenic | -0.013 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/K | 0.2108 | likely_benign | 0.2026 | benign | -0.884 | Destabilizing | 0.997 | D | 0.535 | neutral | N | 0.495789235 | None | None | N |
| R/L | 0.6111 | likely_pathogenic | 0.6347 | pathogenic | -0.013 | Destabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| R/M | 0.7075 | likely_pathogenic | 0.7384 | pathogenic | -0.168 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.485910274 | None | None | N |
| R/N | 0.8861 | likely_pathogenic | 0.8939 | pathogenic | -0.27 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/P | 0.9481 | likely_pathogenic | 0.9556 | pathogenic | -0.255 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/Q | 0.1928 | likely_benign | 0.1934 | benign | -0.509 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/S | 0.8179 | likely_pathogenic | 0.8425 | pathogenic | -1.0 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.463927533 | None | None | N |
| R/T | 0.5745 | likely_pathogenic | 0.6272 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.674 | neutral | N | 0.491172849 | None | None | N |
| R/V | 0.754 | likely_pathogenic | 0.7755 | pathogenic | -0.255 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/W | 0.417 | ambiguous | 0.4444 | ambiguous | -0.465 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.526006351 | None | None | N |
| R/Y | 0.7617 | likely_pathogenic | 0.78 | pathogenic | -0.143 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.