Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26791 | 80596;80597;80598 | chr2:178565761;178565760;178565759 | chr2:179430488;179430487;179430486 |
| N2AB | 25150 | 75673;75674;75675 | chr2:178565761;178565760;178565759 | chr2:179430488;179430487;179430486 |
| N2A | 24223 | 72892;72893;72894 | chr2:178565761;178565760;178565759 | chr2:179430488;179430487;179430486 |
| N2B | 17726 | 53401;53402;53403 | chr2:178565761;178565760;178565759 | chr2:179430488;179430487;179430486 |
| Novex-1 | 17851 | 53776;53777;53778 | chr2:178565761;178565760;178565759 | chr2:179430488;179430487;179430486 |
| Novex-2 | 17918 | 53977;53978;53979 | chr2:178565761;178565760;178565759 | chr2:179430488;179430487;179430486 |
| 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/E | rs749401230  |
0.315 | 0.047 | N | 0.216 | 0.128 | 0.17258766438 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 1.24008E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs749401230 |
0.315 | 0.047 | N | 0.216 | 0.128 | 0.17258766438 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20651E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs749401230 |
0.315 | 0.047 | N | 0.216 | 0.128 | 0.17258766438 | gnomAD-4.0.0 | 4.33841E-06 | None | None | None | None | N | None | 9.34704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | None | None | 0.959 | N | 0.574 | 0.543 | 0.324161360171 | gnomAD-4.0.0 | 1.59171E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76872E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | None | None | 0.999 | N | 0.655 | 0.543 | 0.36036328697 | 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 |
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 | 0.5789 | likely_pathogenic | 0.514 | ambiguous | -0.532 | Destabilizing | 0.97 | D | 0.559 | neutral | N | 0.468722212 | None | None | N |
| D/C | 0.9503 | likely_pathogenic | 0.9449 | pathogenic | 0.084 | Stabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/E | 0.4958 | ambiguous | 0.4273 | ambiguous | -0.325 | Destabilizing | 0.047 | N | 0.216 | neutral | N | 0.500874476 | None | None | N |
| D/F | 0.9441 | likely_pathogenic | 0.9231 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/G | 0.5641 | likely_pathogenic | 0.5118 | ambiguous | -0.751 | Destabilizing | 0.959 | D | 0.574 | neutral | N | 0.481586228 | None | None | N |
| D/H | 0.7872 | likely_pathogenic | 0.7453 | pathogenic | -0.447 | Destabilizing | 0.999 | D | 0.655 | neutral | N | 0.49579337 | None | None | N |
| D/I | 0.9269 | likely_pathogenic | 0.8944 | pathogenic | 0.011 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/K | 0.8982 | likely_pathogenic | 0.8548 | pathogenic | 0.386 | Stabilizing | 0.994 | D | 0.635 | neutral | None | None | None | None | N |
| D/L | 0.8983 | likely_pathogenic | 0.8649 | pathogenic | 0.011 | Stabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/M | 0.9481 | likely_pathogenic | 0.9301 | pathogenic | 0.335 | Stabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| D/N | 0.3036 | likely_benign | 0.2693 | benign | -0.03 | Destabilizing | 0.311 | N | 0.211 | neutral | N | 0.467886064 | None | None | N |
| D/P | 0.9948 | likely_pathogenic | 0.9934 | pathogenic | -0.149 | Destabilizing | 0.985 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/Q | 0.8338 | likely_pathogenic | 0.7823 | pathogenic | 0.011 | Stabilizing | 0.995 | D | 0.632 | neutral | None | None | None | None | N |
| D/R | 0.886 | likely_pathogenic | 0.8354 | pathogenic | 0.434 | Stabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/S | 0.4003 | ambiguous | 0.3409 | ambiguous | -0.134 | Destabilizing | 0.977 | D | 0.485 | neutral | None | None | None | None | N |
| D/T | 0.7497 | likely_pathogenic | 0.6923 | pathogenic | 0.051 | Stabilizing | 0.985 | D | 0.645 | neutral | None | None | None | None | N |
| D/V | 0.7921 | likely_pathogenic | 0.7259 | pathogenic | -0.149 | Destabilizing | 0.993 | D | 0.713 | prob.delet. | N | 0.501932208 | None | None | N |
| D/W | 0.9883 | likely_pathogenic | 0.9848 | pathogenic | -0.235 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/Y | 0.7301 | likely_pathogenic | 0.6725 | pathogenic | -0.168 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.505668418 | 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.