Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6339 | 19240;19241;19242 | chr2:178729023;178729022;178729021 | chr2:179593750;179593749;179593748 |
| N2AB | 6022 | 18289;18290;18291 | chr2:178729023;178729022;178729021 | chr2:179593750;179593749;179593748 |
| N2A | 5095 | 15508;15509;15510 | chr2:178729023;178729022;178729021 | chr2:179593750;179593749;179593748 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs192553687  |
-0.096 | 0.258 | N | 0.381 | 0.19 | None | gnomAD-2.1.1 | 1.1502E-04 | None | None | None | None | I | None | 8.32E-05 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.04905E-04 | 4.25411E-04 |
| Y/C | rs192553687 |
-0.096 | 0.258 | N | 0.381 | 0.19 | None | gnomAD-3.1.2 | 2.10352E-04 | None | None | None | None | I | None | 2.65457E-04 | 1.31044E-04 | 0 | 0 | 1.93199E-04 | None | 0 | 0 | 2.6462E-04 | 0 | 0 |
| Y/C | rs192553687 |
-0.096 | 0.258 | N | 0.381 | 0.19 | None | gnomAD-4.0.0 | 3.65773E-04 | None | None | None | None | I | None | 1.86657E-04 | 5.00969E-05 | None | 0 | 4.46907E-05 | None | 0 | 0 | 4.72228E-04 | 2.19809E-05 | 1.92234E-04 |
| Y/D | None | None | 0.001 | N | 0.387 | 0.266 | 0.311691414656 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.1127 | likely_benign | 0.1139 | benign | -1.719 | Destabilizing | 0.001 | N | 0.359 | neutral | None | None | None | None | I |
| Y/C | 0.0659 | likely_benign | 0.0625 | benign | -0.478 | Destabilizing | 0.258 | N | 0.381 | neutral | N | 0.520186247 | None | None | I |
| Y/D | 0.0775 | likely_benign | 0.0758 | benign | 0.073 | Stabilizing | 0.001 | N | 0.387 | neutral | N | 0.446149849 | None | None | I |
| Y/E | 0.1572 | likely_benign | 0.1504 | benign | 0.116 | Stabilizing | None | N | 0.234 | neutral | None | None | None | None | I |
| Y/F | 0.0759 | likely_benign | 0.0742 | benign | -0.716 | Destabilizing | 0.007 | N | 0.353 | neutral | N | 0.439647951 | None | None | I |
| Y/G | 0.13 | likely_benign | 0.1376 | benign | -1.996 | Destabilizing | None | N | 0.306 | neutral | None | None | None | None | I |
| Y/H | 0.0529 | likely_benign | 0.0552 | benign | -0.478 | Destabilizing | None | N | 0.125 | neutral | N | 0.42646801 | None | None | I |
| Y/I | 0.1208 | likely_benign | 0.1194 | benign | -0.924 | Destabilizing | 0.004 | N | 0.361 | neutral | None | None | None | None | I |
| Y/K | 0.1194 | likely_benign | 0.1264 | benign | -0.624 | Destabilizing | 0.001 | N | 0.394 | neutral | None | None | None | None | I |
| Y/L | 0.1348 | likely_benign | 0.1398 | benign | -0.924 | Destabilizing | None | N | 0.23 | neutral | None | None | None | None | I |
| Y/M | 0.235 | likely_benign | 0.2338 | benign | -0.625 | Destabilizing | 0.021 | N | 0.442 | neutral | None | None | None | None | I |
| Y/N | 0.0514 | likely_benign | 0.0521 | benign | -0.836 | Destabilizing | 0.001 | N | 0.373 | neutral | N | 0.427158656 | None | None | I |
| Y/P | 0.5496 | ambiguous | 0.5723 | pathogenic | -1.177 | Destabilizing | 0.018 | N | 0.457 | neutral | None | None | None | None | I |
| Y/Q | 0.0962 | likely_benign | 0.0975 | benign | -0.791 | Destabilizing | None | N | 0.208 | neutral | None | None | None | None | I |
| Y/R | 0.0725 | likely_benign | 0.0803 | benign | -0.199 | Destabilizing | None | N | 0.267 | neutral | None | None | None | None | I |
| Y/S | 0.0578 | likely_benign | 0.0565 | benign | -1.377 | Destabilizing | 0.001 | N | 0.377 | neutral | N | 0.392950082 | None | None | I |
| Y/T | 0.0927 | likely_benign | 0.0911 | benign | -1.243 | Destabilizing | 0.004 | N | 0.391 | neutral | None | None | None | None | I |
| Y/V | 0.1028 | likely_benign | 0.1027 | benign | -1.177 | Destabilizing | 0.002 | N | 0.308 | neutral | None | None | None | None | I |
| Y/W | 0.2474 | likely_benign | 0.259 | benign | -0.465 | Destabilizing | 0.316 | N | 0.388 | neutral | None | None | 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.