Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2154 | 6685;6686;6687 | chr2:178775404;178775403;178775402 | chr2:179640131;179640130;179640129 |
| N2AB | 2154 | 6685;6686;6687 | chr2:178775404;178775403;178775402 | chr2:179640131;179640130;179640129 |
| N2A | 2154 | 6685;6686;6687 | chr2:178775404;178775403;178775402 | chr2:179640131;179640130;179640129 |
| N2B | 2108 | 6547;6548;6549 | chr2:178775404;178775403;178775402 | chr2:179640131;179640130;179640129 |
| Novex-1 | 2108 | 6547;6548;6549 | chr2:178775404;178775403;178775402 | chr2:179640131;179640130;179640129 |
| Novex-2 | 2108 | 6547;6548;6549 | chr2:178775404;178775403;178775402 | chr2:179640131;179640130;179640129 |
| Novex-3 | 2154 | 6685;6686;6687 | chr2:178775404;178775403;178775402 | chr2:179640131;179640130;179640129 |
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/M | rs780879621  |
-1.009 | 0.019 | N | 0.209 | 0.044 | 0.419957187557 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs780879621 |
-1.009 | 0.019 | N | 0.209 | 0.044 | 0.419957187557 | gnomAD-4.0.0 | 2.73641E-06 | None | None | None | None | N | None | 0 | 8.94614E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2154345699 |
None | None | N | 0.089 | 0.087 | 0.276898752692 | gnomAD-4.0.0 | 2.05229E-06 | None | None | None | None | N | None | 2.98757E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.237 | likely_benign | 0.2548 | benign | -1.997 | Destabilizing | None | N | 0.154 | neutral | None | None | None | None | N |
| I/C | 0.5666 | likely_pathogenic | 0.6011 | pathogenic | -1.179 | Destabilizing | 0.667 | D | 0.469 | neutral | None | None | None | None | N |
| I/D | 0.6946 | likely_pathogenic | 0.7418 | pathogenic | -2.25 | Highly Destabilizing | 0.124 | N | 0.539 | neutral | None | None | None | None | N |
| I/E | 0.4915 | ambiguous | 0.5084 | ambiguous | -2.249 | Highly Destabilizing | 0.22 | N | 0.563 | neutral | None | None | None | None | N |
| I/F | 0.1794 | likely_benign | 0.1906 | benign | -1.542 | Destabilizing | 0.001 | N | 0.189 | neutral | N | 0.484932479 | None | None | N |
| I/G | 0.4894 | ambiguous | 0.5411 | ambiguous | -2.326 | Highly Destabilizing | 0.124 | N | 0.499 | neutral | None | None | None | None | N |
| I/H | 0.4136 | ambiguous | 0.4232 | ambiguous | -1.627 | Destabilizing | 0.667 | D | 0.505 | neutral | None | None | None | None | N |
| I/K | 0.2611 | likely_benign | 0.2425 | benign | -1.391 | Destabilizing | 0.22 | N | 0.56 | neutral | None | None | None | None | N |
| I/L | 0.1175 | likely_benign | 0.1282 | benign | -1.139 | Destabilizing | 0.019 | N | 0.212 | neutral | N | 0.486714188 | None | None | N |
| I/M | 0.0852 | likely_benign | 0.0876 | benign | -0.786 | Destabilizing | 0.019 | N | 0.209 | neutral | N | 0.460940936 | None | None | N |
| I/N | 0.2297 | likely_benign | 0.2323 | benign | -1.238 | Destabilizing | 0.003 | N | 0.405 | neutral | N | 0.467204471 | None | None | N |
| I/P | 0.9699 | likely_pathogenic | 0.9803 | pathogenic | -1.399 | Destabilizing | 0.667 | D | 0.537 | neutral | None | None | None | None | N |
| I/Q | 0.3121 | likely_benign | 0.3183 | benign | -1.48 | Destabilizing | 0.667 | D | 0.541 | neutral | None | None | None | None | N |
| I/R | 0.209 | likely_benign | 0.2044 | benign | -0.749 | Destabilizing | 0.667 | D | 0.531 | neutral | None | None | None | None | N |
| I/S | 0.2011 | likely_benign | 0.2063 | benign | -1.736 | Destabilizing | 0.096 | N | 0.479 | neutral | N | 0.351568157 | None | None | N |
| I/T | 0.1508 | likely_benign | 0.1598 | benign | -1.633 | Destabilizing | 0.081 | N | 0.426 | neutral | N | 0.364804788 | None | None | N |
| I/V | 0.0614 | likely_benign | 0.0635 | benign | -1.399 | Destabilizing | None | N | 0.089 | neutral | N | 0.442061572 | None | None | N |
| I/W | 0.7511 | likely_pathogenic | 0.8077 | pathogenic | -1.68 | Destabilizing | 0.958 | D | 0.503 | neutral | None | None | None | None | N |
| I/Y | 0.4973 | ambiguous | 0.5276 | ambiguous | -1.472 | Destabilizing | 0.331 | N | 0.485 | 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.