Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24935 | 75028;75029;75030 | chr2:178571329;178571328;178571327 | chr2:179436056;179436055;179436054 |
| N2AB | 23294 | 70105;70106;70107 | chr2:178571329;178571328;178571327 | chr2:179436056;179436055;179436054 |
| N2A | 22367 | 67324;67325;67326 | chr2:178571329;178571328;178571327 | chr2:179436056;179436055;179436054 |
| N2B | 15870 | 47833;47834;47835 | chr2:178571329;178571328;178571327 | chr2:179436056;179436055;179436054 |
| Novex-1 | 15995 | 48208;48209;48210 | chr2:178571329;178571328;178571327 | chr2:179436056;179436055;179436054 |
| Novex-2 | 16062 | 48409;48410;48411 | chr2:178571329;178571328;178571327 | chr2:179436056;179436055;179436054 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 1.0 | N | 0.706 | 0.534 | 0.450248222533 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| D/G | None | None | 1.0 | N | 0.706 | 0.534 | 0.450248222533 | gnomAD-4.0.0 | 2.73731E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59837E-06 | 0 | 0 |
| D/N | None | None | 1.0 | N | 0.699 | 0.42 | 0.415055319159 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.735 | likely_pathogenic | 0.7428 | pathogenic | -0.312 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.49618499 | None | None | I |
| D/C | 0.9289 | likely_pathogenic | 0.9371 | pathogenic | 0.248 | Stabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | I |
| D/E | 0.77 | likely_pathogenic | 0.7939 | pathogenic | -0.499 | Destabilizing | 1.0 | D | 0.441 | neutral | N | 0.490068924 | None | None | I |
| D/F | 0.9666 | likely_pathogenic | 0.9686 | pathogenic | -0.586 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| D/G | 0.6714 | likely_pathogenic | 0.6863 | pathogenic | -0.524 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.513835173 | None | None | I |
| D/H | 0.8276 | likely_pathogenic | 0.8311 | pathogenic | -0.847 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.496945459 | None | None | I |
| D/I | 0.9268 | likely_pathogenic | 0.9353 | pathogenic | 0.203 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| D/K | 0.93 | likely_pathogenic | 0.9355 | pathogenic | 0.331 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/L | 0.9149 | likely_pathogenic | 0.9238 | pathogenic | 0.203 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/M | 0.9626 | likely_pathogenic | 0.9656 | pathogenic | 0.634 | Stabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | I |
| D/N | 0.1396 | likely_benign | 0.15 | benign | 0.078 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.492604496 | None | None | I |
| D/P | 0.9575 | likely_pathogenic | 0.9634 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | I |
| D/Q | 0.9175 | likely_pathogenic | 0.9206 | pathogenic | 0.101 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | I |
| D/R | 0.9316 | likely_pathogenic | 0.934 | pathogenic | 0.197 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/S | 0.3375 | likely_benign | 0.3324 | benign | -0.032 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/T | 0.4968 | ambiguous | 0.5078 | ambiguous | 0.141 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| D/V | 0.8189 | likely_pathogenic | 0.8412 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.510098963 | None | None | I |
| D/W | 0.9939 | likely_pathogenic | 0.9938 | pathogenic | -0.556 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| D/Y | 0.7981 | likely_pathogenic | 0.8057 | pathogenic | -0.362 | Destabilizing | 1.0 | D | 0.63 | neutral | D | 0.543295733 | 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.