Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24780 | 74563;74564;74565 | chr2:178571794;178571793;178571792 | chr2:179436521;179436520;179436519 |
| N2AB | 23139 | 69640;69641;69642 | chr2:178571794;178571793;178571792 | chr2:179436521;179436520;179436519 |
| N2A | 22212 | 66859;66860;66861 | chr2:178571794;178571793;178571792 | chr2:179436521;179436520;179436519 |
| N2B | 15715 | 47368;47369;47370 | chr2:178571794;178571793;178571792 | chr2:179436521;179436520;179436519 |
| Novex-1 | 15840 | 47743;47744;47745 | chr2:178571794;178571793;178571792 | chr2:179436521;179436520;179436519 |
| Novex-2 | 15907 | 47944;47945;47946 | chr2:178571794;178571793;178571792 | chr2:179436521;179436520;179436519 |
| 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/Q | rs776673912  |
0.116 | 0.994 | N | 0.407 | 0.246 | 0.193865811164 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 1.66168E-04 |
| R/Q | rs776673912 |
0.116 | 0.994 | N | 0.407 | 0.246 | 0.193865811164 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs776673912 |
0.116 | 0.994 | N | 0.407 | 0.246 | 0.193865811164 | gnomAD-4.0.0 | 8.67764E-06 | None | None | None | None | I | None | 0 | 1.66744E-05 | None | 0 | 0 | None | 0 | 0 | 5.08647E-06 | 5.49282E-05 | 3.20307E-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 | 0.3397 | likely_benign | 0.3709 | ambiguous | 0.099 | Stabilizing | 0.919 | D | 0.434 | neutral | None | None | None | None | I |
| R/C | 0.2226 | likely_benign | 0.2463 | benign | -0.139 | Destabilizing | 0.999 | D | 0.586 | neutral | None | None | None | None | I |
| R/D | 0.731 | likely_pathogenic | 0.7924 | pathogenic | -0.245 | Destabilizing | 0.976 | D | 0.447 | neutral | None | None | None | None | I |
| R/E | 0.3547 | ambiguous | 0.3796 | ambiguous | -0.197 | Destabilizing | 0.851 | D | 0.415 | neutral | None | None | None | None | I |
| R/F | 0.5858 | likely_pathogenic | 0.6268 | pathogenic | -0.202 | Destabilizing | 0.996 | D | 0.547 | neutral | None | None | None | None | I |
| R/G | 0.259 | likely_benign | 0.3029 | benign | -0.055 | Destabilizing | 0.956 | D | 0.408 | neutral | N | 0.469721446 | None | None | I |
| R/H | 0.1428 | likely_benign | 0.1664 | benign | -0.601 | Destabilizing | 0.996 | D | 0.415 | neutral | None | None | None | None | I |
| R/I | 0.2358 | likely_benign | 0.2517 | benign | 0.462 | Stabilizing | 0.988 | D | 0.556 | neutral | None | None | None | None | I |
| R/K | 0.0832 | likely_benign | 0.0823 | benign | -0.059 | Destabilizing | 0.015 | N | 0.233 | neutral | None | None | None | None | I |
| R/L | 0.2474 | likely_benign | 0.2666 | benign | 0.462 | Stabilizing | 0.956 | D | 0.408 | neutral | N | 0.500420611 | None | None | I |
| R/M | 0.2489 | likely_benign | 0.2643 | benign | -0.002 | Destabilizing | 0.999 | D | 0.435 | neutral | None | None | None | None | I |
| R/N | 0.5762 | likely_pathogenic | 0.6701 | pathogenic | 0.055 | Stabilizing | 0.976 | D | 0.381 | neutral | None | None | None | None | I |
| R/P | 0.4291 | ambiguous | 0.4645 | ambiguous | 0.36 | Stabilizing | 0.994 | D | 0.509 | neutral | N | 0.498151097 | None | None | I |
| R/Q | 0.1039 | likely_benign | 0.1124 | benign | 0.015 | Stabilizing | 0.994 | D | 0.407 | neutral | N | 0.45595883 | None | None | I |
| R/S | 0.4659 | ambiguous | 0.5315 | ambiguous | -0.134 | Destabilizing | 0.919 | D | 0.425 | neutral | None | None | None | None | I |
| R/T | 0.2408 | likely_benign | 0.2715 | benign | 0.027 | Stabilizing | 0.919 | D | 0.389 | neutral | None | None | None | None | I |
| R/V | 0.308 | likely_benign | 0.321 | benign | 0.36 | Stabilizing | 0.988 | D | 0.556 | neutral | None | None | None | None | I |
| R/W | 0.2203 | likely_benign | 0.2412 | benign | -0.38 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | I |
| R/Y | 0.4707 | ambiguous | 0.5169 | ambiguous | 0.038 | Stabilizing | 0.996 | D | 0.503 | neutral | None | None | None | None | I |
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.