Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23596 | 71011;71012;71013 | chr2:178575346;178575345;178575344 | chr2:179440073;179440072;179440071 |
| N2AB | 21955 | 66088;66089;66090 | chr2:178575346;178575345;178575344 | chr2:179440073;179440072;179440071 |
| N2A | 21028 | 63307;63308;63309 | chr2:178575346;178575345;178575344 | chr2:179440073;179440072;179440071 |
| N2B | 14531 | 43816;43817;43818 | chr2:178575346;178575345;178575344 | chr2:179440073;179440072;179440071 |
| Novex-1 | 14656 | 44191;44192;44193 | chr2:178575346;178575345;178575344 | chr2:179440073;179440072;179440071 |
| Novex-2 | 14723 | 44392;44393;44394 | chr2:178575346;178575345;178575344 | chr2:179440073;179440072;179440071 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs574577289  |
-1.039 | 0.081 | N | 0.273 | 0.089 | 0.15556083564 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs574577289 |
-1.039 | 0.081 | N | 0.273 | 0.089 | 0.15556083564 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs574577289 |
-1.039 | 0.081 | N | 0.273 | 0.089 | 0.15556083564 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/A | rs574577289 |
-1.039 | 0.081 | N | 0.273 | 0.089 | 0.15556083564 | gnomAD-4.0.0 | 6.56728E-06 | None | None | None | None | N | None | 2.40512E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0771 | likely_benign | 0.0774 | benign | -0.797 | Destabilizing | 0.081 | N | 0.273 | neutral | N | 0.485734452 | None | None | N |
| T/C | 0.3756 | ambiguous | 0.3848 | ambiguous | -0.54 | Destabilizing | 0.958 | D | 0.359 | neutral | None | None | None | None | N |
| T/D | 0.3904 | ambiguous | 0.3772 | ambiguous | 0.316 | Stabilizing | 0.124 | N | 0.359 | neutral | None | None | None | None | N |
| T/E | 0.2708 | likely_benign | 0.2619 | benign | 0.313 | Stabilizing | 0.055 | N | 0.345 | neutral | None | None | None | None | N |
| T/F | 0.2528 | likely_benign | 0.2495 | benign | -1.066 | Destabilizing | 0.497 | N | 0.393 | neutral | None | None | None | None | N |
| T/G | 0.2367 | likely_benign | 0.2416 | benign | -1.015 | Destabilizing | 0.055 | N | 0.366 | neutral | None | None | None | None | N |
| T/H | 0.2084 | likely_benign | 0.2112 | benign | -1.135 | Destabilizing | 0.667 | D | 0.38 | neutral | None | None | None | None | N |
| T/I | 0.1204 | likely_benign | 0.1213 | benign | -0.318 | Destabilizing | 0.096 | N | 0.336 | neutral | N | 0.47592289 | None | None | N |
| T/K | 0.1815 | likely_benign | 0.1673 | benign | -0.432 | Destabilizing | 0.055 | N | 0.346 | neutral | None | None | None | None | N |
| T/L | 0.088 | likely_benign | 0.0855 | benign | -0.318 | Destabilizing | 0.055 | N | 0.363 | neutral | None | None | None | None | N |
| T/M | 0.0863 | likely_benign | 0.0878 | benign | -0.23 | Destabilizing | 0.025 | N | 0.263 | neutral | None | None | None | None | N |
| T/N | 0.1044 | likely_benign | 0.1037 | benign | -0.421 | Destabilizing | None | N | 0.097 | neutral | N | 0.464532461 | None | None | N |
| T/P | 0.2118 | likely_benign | 0.1749 | benign | -0.447 | Destabilizing | 0.602 | D | 0.43 | neutral | N | 0.506707157 | None | None | N |
| T/Q | 0.1832 | likely_benign | 0.1834 | benign | -0.515 | Destabilizing | 0.004 | N | 0.19 | neutral | None | None | None | None | N |
| T/R | 0.1604 | likely_benign | 0.1462 | benign | -0.218 | Destabilizing | 0.001 | N | 0.199 | neutral | None | None | None | None | N |
| T/S | 0.1035 | likely_benign | 0.1044 | benign | -0.759 | Destabilizing | 0.042 | N | 0.301 | neutral | N | 0.44398383 | None | None | N |
| T/V | 0.0979 | likely_benign | 0.1015 | benign | -0.447 | Destabilizing | 0.002 | N | 0.103 | neutral | None | None | None | None | N |
| T/W | 0.5705 | likely_pathogenic | 0.5629 | ambiguous | -1.012 | Destabilizing | 0.958 | D | 0.392 | neutral | None | None | None | None | N |
| T/Y | 0.2905 | likely_benign | 0.2864 | benign | -0.744 | Destabilizing | 0.667 | D | 0.379 | 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.