Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25370 | 76333;76334;76335 | chr2:178570024;178570023;178570022 | chr2:179434751;179434750;179434749 |
| N2AB | 23729 | 71410;71411;71412 | chr2:178570024;178570023;178570022 | chr2:179434751;179434750;179434749 |
| N2A | 22802 | 68629;68630;68631 | chr2:178570024;178570023;178570022 | chr2:179434751;179434750;179434749 |
| N2B | 16305 | 49138;49139;49140 | chr2:178570024;178570023;178570022 | chr2:179434751;179434750;179434749 |
| Novex-1 | 16430 | 49513;49514;49515 | chr2:178570024;178570023;178570022 | chr2:179434751;179434750;179434749 |
| Novex-2 | 16497 | 49714;49715;49716 | chr2:178570024;178570023;178570022 | chr2:179434751;179434750;179434749 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs751411453  |
-0.609 | None | N | 0.097 | 0.094 | 0.0716867268079 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/L | rs751411453 |
-0.609 | None | N | 0.097 | 0.094 | 0.0716867268079 | gnomAD-4.0.0 | 1.59254E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86026E-06 | 0 | 0 |
| I/T | rs764131874 |
-0.995 | 0.117 | N | 0.355 | 0.14 | 0.504113619024 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs764131874 |
-0.995 | 0.117 | N | 0.355 | 0.14 | 0.504113619024 | gnomAD-4.0.0 | 6.84439E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52461E-05 | None | 0 | 0 | 7.19721E-06 | 0 | 1.65695E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1375 | likely_benign | 0.1175 | benign | -1.629 | Destabilizing | 0.035 | N | 0.341 | neutral | None | None | None | None | N |
| I/C | 0.5485 | ambiguous | 0.51 | ambiguous | -0.809 | Destabilizing | 0.935 | D | 0.314 | neutral | None | None | None | None | N |
| I/D | 0.6791 | likely_pathogenic | 0.6529 | pathogenic | -1.141 | Destabilizing | 0.38 | N | 0.346 | neutral | None | None | None | None | N |
| I/E | 0.4988 | ambiguous | 0.4603 | ambiguous | -1.135 | Destabilizing | 0.081 | N | 0.388 | neutral | None | None | None | None | N |
| I/F | 0.1465 | likely_benign | 0.1263 | benign | -1.176 | Destabilizing | 0.235 | N | 0.295 | neutral | None | None | None | None | N |
| I/G | 0.3928 | ambiguous | 0.3532 | ambiguous | -1.946 | Destabilizing | 0.262 | N | 0.367 | neutral | None | None | None | None | N |
| I/H | 0.3516 | ambiguous | 0.3039 | benign | -1.057 | Destabilizing | 0.824 | D | 0.307 | neutral | None | None | None | None | N |
| I/K | 0.2875 | likely_benign | 0.2547 | benign | -1.045 | Destabilizing | 0.062 | N | 0.373 | neutral | N | 0.435668204 | None | None | N |
| I/L | 0.0527 | likely_benign | 0.051 | benign | -0.83 | Destabilizing | None | N | 0.097 | neutral | N | 0.44881086 | None | None | N |
| I/M | 0.0608 | likely_benign | 0.0572 | benign | -0.594 | Destabilizing | 0.188 | N | 0.341 | neutral | N | 0.488081324 | None | None | N |
| I/N | 0.2231 | likely_benign | 0.2138 | benign | -0.855 | Destabilizing | 0.555 | D | 0.349 | neutral | None | None | None | None | N |
| I/P | 0.5644 | likely_pathogenic | 0.4976 | ambiguous | -1.066 | Destabilizing | 0.791 | D | 0.349 | neutral | None | None | None | None | N |
| I/Q | 0.2413 | likely_benign | 0.205 | benign | -1.037 | Destabilizing | 0.016 | N | 0.323 | neutral | None | None | None | None | N |
| I/R | 0.2053 | likely_benign | 0.1744 | benign | -0.404 | Destabilizing | 0.317 | N | 0.345 | neutral | N | 0.470319495 | None | None | N |
| I/S | 0.1715 | likely_benign | 0.1558 | benign | -1.427 | Destabilizing | 0.149 | N | 0.394 | neutral | None | None | None | None | N |
| I/T | 0.0758 | likely_benign | 0.0745 | benign | -1.304 | Destabilizing | 0.117 | N | 0.355 | neutral | N | 0.401248986 | None | None | N |
| I/V | 0.0687 | likely_benign | 0.0692 | benign | -1.066 | Destabilizing | None | N | 0.095 | neutral | N | 0.472053079 | None | None | N |
| I/W | 0.5579 | ambiguous | 0.4797 | ambiguous | -1.246 | Destabilizing | 0.935 | D | 0.324 | neutral | None | None | None | None | N |
| I/Y | 0.4492 | ambiguous | 0.3909 | ambiguous | -1.027 | Destabilizing | 0.555 | D | 0.331 | 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.