Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27300 | 82123;82124;82125 | chr2:178564234;178564233;178564232 | chr2:179428961;179428960;179428959 |
| N2AB | 25659 | 77200;77201;77202 | chr2:178564234;178564233;178564232 | chr2:179428961;179428960;179428959 |
| N2A | 24732 | 74419;74420;74421 | chr2:178564234;178564233;178564232 | chr2:179428961;179428960;179428959 |
| N2B | 18235 | 54928;54929;54930 | chr2:178564234;178564233;178564232 | chr2:179428961;179428960;179428959 |
| Novex-1 | 18360 | 55303;55304;55305 | chr2:178564234;178564233;178564232 | chr2:179428961;179428960;179428959 |
| Novex-2 | 18427 | 55504;55505;55506 | chr2:178564234;178564233;178564232 | chr2:179428961;179428960;179428959 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs372530032  |
-0.025 | 0.877 | D | 0.238 | 0.352 | None | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 2.68E-05 | 0 |
| R/C | rs372530032 |
-0.025 | 0.877 | D | 0.238 | 0.352 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs372530032 |
-0.025 | 0.877 | D | 0.238 | 0.352 | None | gnomAD-4.0.0 | 1.79772E-05 | None | None | None | None | I | None | 0 | 5.00117E-05 | None | 0 | 0 | None | 0 | 0 | 1.94956E-05 | 2.19587E-05 | 1.60123E-05 |
| R/H | rs55850344 |
-0.735 | None | N | 0.081 | 0.069 | None | gnomAD-2.1.1 | 3.58069E-04 | None | None | None | None | I | None | 2.8928E-04 | 3.11156E-04 | None | 0 | 1.02564E-04 | None | 4.24837E-04 | None | 3.64225E-04 | 4.47122E-04 | 1.40568E-04 |
| R/H | rs55850344 |
-0.735 | None | N | 0.081 | 0.069 | None | gnomAD-3.1.2 | 3.48409E-04 | None | None | None | None | I | None | 2.89659E-04 | 2.6202E-04 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 5.29303E-04 | 0 | 0 |
| R/H | rs55850344 |
-0.735 | None | N | 0.081 | 0.069 | None | gnomAD-4.0.0 | 4.20878E-04 | None | None | None | None | I | None | 3.33244E-04 | 2.83296E-04 | None | 3.37906E-05 | 0 | None | 3.62113E-04 | 6.60066E-04 | 4.67889E-04 | 3.73282E-04 | 3.68141E-04 |
| R/L | None | None | 0.058 | N | 0.202 | 0.16 | 0.346085882481 | gnomAD-4.0.0 | 6.84436E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99473E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2242 | likely_benign | 0.2271 | benign | 0.007 | Stabilizing | None | N | 0.11 | neutral | None | None | None | None | I |
| R/C | 0.0987 | likely_benign | 0.0941 | benign | -0.333 | Destabilizing | 0.877 | D | 0.238 | neutral | D | 0.53665721 | None | None | I |
| R/D | 0.4055 | ambiguous | 0.3621 | ambiguous | -0.387 | Destabilizing | 0.072 | N | 0.319 | neutral | None | None | None | None | I |
| R/E | 0.2583 | likely_benign | 0.2507 | benign | -0.354 | Destabilizing | 0.016 | N | 0.173 | neutral | None | None | None | None | I |
| R/F | 0.2546 | likely_benign | 0.2355 | benign | -0.343 | Destabilizing | 0.038 | N | 0.363 | neutral | None | None | None | None | I |
| R/G | 0.1549 | likely_benign | 0.1568 | benign | -0.11 | Destabilizing | 0.03 | N | 0.213 | neutral | N | 0.458292427 | None | None | I |
| R/H | 0.0633 | likely_benign | 0.0612 | benign | -0.596 | Destabilizing | None | N | 0.081 | neutral | N | 0.436917077 | None | None | I |
| R/I | 0.1781 | likely_benign | 0.1829 | benign | 0.267 | Stabilizing | 0.072 | N | 0.365 | neutral | None | None | None | None | I |
| R/K | 0.1152 | likely_benign | 0.1188 | benign | -0.254 | Destabilizing | 0.031 | N | 0.196 | neutral | None | None | None | None | I |
| R/L | 0.1458 | likely_benign | 0.1385 | benign | 0.267 | Stabilizing | 0.058 | N | 0.202 | neutral | N | 0.44842215 | None | None | I |
| R/M | 0.2234 | likely_benign | 0.2453 | benign | -0.164 | Destabilizing | 0.628 | D | 0.268 | neutral | None | None | None | None | I |
| R/N | 0.2827 | likely_benign | 0.2549 | benign | -0.204 | Destabilizing | 0.016 | N | 0.193 | neutral | None | None | None | None | I |
| R/P | 0.857 | likely_pathogenic | 0.8341 | pathogenic | 0.197 | Stabilizing | 0.232 | N | 0.368 | neutral | D | 0.536310493 | None | None | I |
| R/Q | 0.0827 | likely_benign | 0.085 | benign | -0.218 | Destabilizing | 0.072 | N | 0.248 | neutral | None | None | None | None | I |
| R/S | 0.2247 | likely_benign | 0.214 | benign | -0.334 | Destabilizing | 0.013 | N | 0.207 | neutral | N | 0.403879152 | None | None | I |
| R/T | 0.1532 | likely_benign | 0.1566 | benign | -0.207 | Destabilizing | None | N | 0.101 | neutral | None | None | None | None | I |
| R/V | 0.2371 | likely_benign | 0.2358 | benign | 0.197 | Stabilizing | 0.031 | N | 0.23 | neutral | None | None | None | None | I |
| R/W | 0.1156 | likely_benign | 0.1157 | benign | -0.562 | Destabilizing | 0.628 | D | 0.226 | neutral | None | None | None | None | I |
| R/Y | 0.1617 | likely_benign | 0.1407 | benign | -0.166 | Destabilizing | None | N | 0.166 | 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.