Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31177 | 93754;93755;93756 | chr2:178548097;178548096;178548095 | chr2:179412824;179412823;179412822 |
| N2AB | 29536 | 88831;88832;88833 | chr2:178548097;178548096;178548095 | chr2:179412824;179412823;179412822 |
| N2A | 28609 | 86050;86051;86052 | chr2:178548097;178548096;178548095 | chr2:179412824;179412823;179412822 |
| N2B | 22112 | 66559;66560;66561 | chr2:178548097;178548096;178548095 | chr2:179412824;179412823;179412822 |
| Novex-1 | 22237 | 66934;66935;66936 | chr2:178548097;178548096;178548095 | chr2:179412824;179412823;179412822 |
| Novex-2 | 22304 | 67135;67136;67137 | chr2:178548097;178548096;178548095 | chr2:179412824;179412823;179412822 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | None | None | 0.81 | N | 0.38 | 0.123 | 0.301789629655 | gnomAD-4.0.0 | 6.84177E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-07 | 0 | 0 |
| V/I | rs769528066  |
-0.364 | 0.004 | N | 0.132 | 0.117 | 0.0986583533028 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0774 | likely_benign | 0.0852 | benign | -0.936 | Destabilizing | 0.201 | N | 0.333 | neutral | N | 0.459105211 | None | None | N |
| V/C | 0.5895 | likely_pathogenic | 0.6302 | pathogenic | -0.896 | Destabilizing | 0.992 | D | 0.388 | neutral | None | None | None | None | N |
| V/D | 0.1821 | likely_benign | 0.175 | benign | -0.148 | Destabilizing | 0.81 | D | 0.443 | neutral | N | 0.469687564 | None | None | N |
| V/E | 0.1417 | likely_benign | 0.1287 | benign | -0.155 | Destabilizing | 0.85 | D | 0.417 | neutral | None | None | None | None | N |
| V/F | 0.1485 | likely_benign | 0.1507 | benign | -0.642 | Destabilizing | 0.81 | D | 0.38 | neutral | N | 0.480155274 | None | None | N |
| V/G | 0.1354 | likely_benign | 0.1363 | benign | -1.215 | Destabilizing | 0.549 | D | 0.39 | neutral | N | 0.479104239 | None | None | N |
| V/H | 0.3069 | likely_benign | 0.3309 | benign | -0.562 | Destabilizing | 0.992 | D | 0.451 | neutral | None | None | None | None | N |
| V/I | 0.0726 | likely_benign | 0.079 | benign | -0.299 | Destabilizing | 0.004 | N | 0.132 | neutral | N | 0.412930204 | None | None | N |
| V/K | 0.1652 | likely_benign | 0.1606 | benign | -0.686 | Destabilizing | 0.85 | D | 0.403 | neutral | None | None | None | None | N |
| V/L | 0.1067 | likely_benign | 0.1138 | benign | -0.299 | Destabilizing | 0.004 | N | 0.179 | neutral | N | 0.454718112 | None | None | N |
| V/M | 0.0969 | likely_benign | 0.1055 | benign | -0.444 | Destabilizing | 0.85 | D | 0.383 | neutral | None | None | None | None | N |
| V/N | 0.1311 | likely_benign | 0.1484 | benign | -0.576 | Destabilizing | 0.85 | D | 0.452 | neutral | None | None | None | None | N |
| V/P | 0.3491 | ambiguous | 0.3433 | ambiguous | -0.474 | Destabilizing | 0.92 | D | 0.437 | neutral | None | None | None | None | N |
| V/Q | 0.1509 | likely_benign | 0.1519 | benign | -0.672 | Destabilizing | 0.92 | D | 0.436 | neutral | None | None | None | None | N |
| V/R | 0.1585 | likely_benign | 0.1407 | benign | -0.264 | Destabilizing | 0.85 | D | 0.456 | neutral | None | None | None | None | N |
| V/S | 0.1018 | likely_benign | 0.1082 | benign | -1.165 | Destabilizing | 0.127 | N | 0.251 | neutral | None | None | None | None | N |
| V/T | 0.078 | likely_benign | 0.0887 | benign | -1.044 | Destabilizing | 0.005 | N | 0.104 | neutral | None | None | None | None | N |
| V/W | 0.6262 | likely_pathogenic | 0.6181 | pathogenic | -0.763 | Destabilizing | 0.992 | D | 0.557 | neutral | None | None | None | None | N |
| V/Y | 0.4109 | ambiguous | 0.4267 | ambiguous | -0.457 | Destabilizing | 0.92 | D | 0.388 | 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.