Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25374 | 76345;76346;76347 | chr2:178570012;178570011;178570010 | chr2:179434739;179434738;179434737 |
| N2AB | 23733 | 71422;71423;71424 | chr2:178570012;178570011;178570010 | chr2:179434739;179434738;179434737 |
| N2A | 22806 | 68641;68642;68643 | chr2:178570012;178570011;178570010 | chr2:179434739;179434738;179434737 |
| N2B | 16309 | 49150;49151;49152 | chr2:178570012;178570011;178570010 | chr2:179434739;179434738;179434737 |
| Novex-1 | 16434 | 49525;49526;49527 | chr2:178570012;178570011;178570010 | chr2:179434739;179434738;179434737 |
| Novex-2 | 16501 | 49726;49727;49728 | chr2:178570012;178570011;178570010 | chr2:179434739;179434738;179434737 |
| 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 | 0.012 | N | 0.389 | 0.078 | 0.178374595973 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/H | None | None | 0.001 | N | 0.291 | 0.104 | 0.0482279557977 | gnomAD-4.0.0 | 6.84549E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16025E-05 | 0 |
| D/N | rs368715583  |
-1.695 | None | N | 0.107 | 0.116 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.94E-06 | 0 |
| D/N | rs368715583 |
-1.695 | None | N | 0.107 | 0.116 | 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 |
| D/N | rs368715583 |
-1.695 | None | N | 0.107 | 0.116 | None | gnomAD-4.0.0 | 1.11604E-05 | None | None | None | None | N | None | 4.00769E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01748E-05 | 2.19751E-05 | 1.60185E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1158 | likely_benign | 0.1124 | benign | -1.042 | Destabilizing | 0.012 | N | 0.419 | neutral | N | 0.431073248 | None | None | N |
| D/C | 0.3028 | likely_benign | 0.2383 | benign | -0.684 | Destabilizing | 0.676 | D | 0.525 | neutral | None | None | None | None | N |
| D/E | 0.1204 | likely_benign | 0.111 | benign | -0.813 | Destabilizing | 0.012 | N | 0.333 | neutral | N | 0.3088589 | None | None | N |
| D/F | 0.3004 | likely_benign | 0.2605 | benign | -0.723 | Destabilizing | 0.214 | N | 0.53 | neutral | None | None | None | None | N |
| D/G | 0.1978 | likely_benign | 0.1811 | benign | -1.45 | Destabilizing | 0.012 | N | 0.389 | neutral | N | 0.453142031 | None | None | N |
| D/H | 0.1515 | likely_benign | 0.1148 | benign | -1.073 | Destabilizing | 0.001 | N | 0.291 | neutral | N | 0.485099734 | None | None | N |
| D/I | 0.1726 | likely_benign | 0.1454 | benign | 0.085 | Stabilizing | None | N | 0.424 | neutral | None | None | None | None | N |
| D/K | 0.3173 | likely_benign | 0.2391 | benign | -1.637 | Destabilizing | 0.038 | N | 0.421 | neutral | None | None | None | None | N |
| D/L | 0.1936 | likely_benign | 0.1707 | benign | 0.085 | Stabilizing | None | N | 0.434 | neutral | None | None | None | None | N |
| D/M | 0.3304 | likely_benign | 0.2808 | benign | 0.833 | Stabilizing | 0.214 | N | 0.539 | neutral | None | None | None | None | N |
| D/N | 0.0698 | likely_benign | 0.0669 | benign | -1.836 | Destabilizing | None | N | 0.107 | neutral | N | 0.442962323 | None | None | N |
| D/P | 0.6343 | likely_pathogenic | 0.5728 | pathogenic | -0.269 | Destabilizing | 0.356 | N | 0.498 | neutral | None | None | None | None | N |
| D/Q | 0.2017 | likely_benign | 0.1758 | benign | -1.502 | Destabilizing | 0.072 | N | 0.436 | neutral | None | None | None | None | N |
| D/R | 0.3359 | likely_benign | 0.2634 | benign | -1.527 | Destabilizing | 0.072 | N | 0.543 | neutral | None | None | None | None | N |
| D/S | 0.0794 | likely_benign | 0.0746 | benign | -2.407 | Highly Destabilizing | None | N | 0.099 | neutral | None | None | None | None | N |
| D/T | 0.13 | likely_benign | 0.1131 | benign | -2.052 | Highly Destabilizing | 0.016 | N | 0.421 | neutral | None | None | None | None | N |
| D/V | 0.1329 | likely_benign | 0.1236 | benign | -0.269 | Destabilizing | 0.004 | N | 0.458 | neutral | N | 0.426648863 | None | None | N |
| D/W | 0.7095 | likely_pathogenic | 0.6288 | pathogenic | -0.854 | Destabilizing | 0.864 | D | 0.569 | neutral | None | None | None | None | N |
| D/Y | 0.125 | likely_benign | 0.104 | benign | -0.631 | Destabilizing | 0.344 | N | 0.532 | neutral | N | 0.448448287 | 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.