Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28316 | 85171;85172;85173 | chr2:178561186;178561185;178561184 | chr2:179425913;179425912;179425911 |
| N2AB | 26675 | 80248;80249;80250 | chr2:178561186;178561185;178561184 | chr2:179425913;179425912;179425911 |
| N2A | 25748 | 77467;77468;77469 | chr2:178561186;178561185;178561184 | chr2:179425913;179425912;179425911 |
| N2B | 19251 | 57976;57977;57978 | chr2:178561186;178561185;178561184 | chr2:179425913;179425912;179425911 |
| Novex-1 | 19376 | 58351;58352;58353 | chr2:178561186;178561185;178561184 | chr2:179425913;179425912;179425911 |
| Novex-2 | 19443 | 58552;58553;58554 | chr2:178561186;178561185;178561184 | chr2:179425913;179425912;179425911 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | None | None | 0.285 | N | 0.314 | 0.241 | 0.258779203287 | gnomAD-4.0.0 | 6.84317E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99446E-07 | 0 | 0 |
| E/Q | rs183238138  |
0.463 | 0.662 | N | 0.398 | 0.184 | None | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 3.71962E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40528E-04 |
| E/Q | rs183238138 |
0.463 | 0.662 | N | 0.398 | 0.184 | None | gnomAD-3.1.2 | 9.86E-05 | None | None | None | None | N | None | 3.13646E-04 | 1.30959E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/Q | rs183238138 |
0.463 | 0.662 | N | 0.398 | 0.184 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| E/Q | rs183238138 |
0.463 | 0.662 | N | 0.398 | 0.184 | None | gnomAD-4.0.0 | 1.79727E-05 | None | None | None | None | N | None | 3.33156E-04 | 3.33311E-05 | None | 0 | 0 | None | 0 | 0 | 8.47601E-07 | 0 | 1.60087E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1786 | likely_benign | 0.1431 | benign | -0.173 | Destabilizing | 0.001 | N | 0.183 | neutral | N | 0.416274367 | None | None | N |
| E/C | 0.8733 | likely_pathogenic | 0.8401 | pathogenic | -0.106 | Destabilizing | 0.991 | D | 0.422 | neutral | None | None | None | None | N |
| E/D | 0.1005 | likely_benign | 0.0915 | benign | -0.256 | Destabilizing | 0.285 | N | 0.345 | neutral | N | 0.343120616 | None | None | N |
| E/F | 0.8774 | likely_pathogenic | 0.8411 | pathogenic | -0.089 | Destabilizing | 0.965 | D | 0.467 | neutral | None | None | None | None | N |
| E/G | 0.1271 | likely_benign | 0.1002 | benign | -0.327 | Destabilizing | None | N | 0.194 | neutral | N | 0.277759628 | None | None | N |
| E/H | 0.5912 | likely_pathogenic | 0.5103 | ambiguous | 0.393 | Stabilizing | 0.965 | D | 0.383 | neutral | None | None | None | None | N |
| E/I | 0.6929 | likely_pathogenic | 0.6418 | pathogenic | 0.185 | Stabilizing | 0.818 | D | 0.473 | neutral | None | None | None | None | N |
| E/K | 0.3763 | ambiguous | 0.2917 | benign | 0.472 | Stabilizing | 0.285 | N | 0.314 | neutral | N | 0.405614656 | None | None | N |
| E/L | 0.6224 | likely_pathogenic | 0.5502 | ambiguous | 0.185 | Stabilizing | 0.561 | D | 0.466 | neutral | None | None | None | None | N |
| E/M | 0.6334 | likely_pathogenic | 0.577 | pathogenic | 0.079 | Stabilizing | 0.965 | D | 0.403 | neutral | None | None | None | None | N |
| E/N | 0.2459 | likely_benign | 0.2017 | benign | 0.124 | Stabilizing | 0.561 | D | 0.325 | neutral | None | None | None | None | N |
| E/P | 0.8306 | likely_pathogenic | 0.7337 | pathogenic | 0.085 | Stabilizing | 0.722 | D | 0.449 | neutral | None | None | None | None | N |
| E/Q | 0.2192 | likely_benign | 0.1784 | benign | 0.154 | Stabilizing | 0.662 | D | 0.398 | neutral | N | 0.451291018 | None | None | N |
| E/R | 0.5257 | ambiguous | 0.4192 | ambiguous | 0.706 | Stabilizing | 0.722 | D | 0.367 | neutral | None | None | None | None | N |
| E/S | 0.1891 | likely_benign | 0.1483 | benign | -0.01 | Destabilizing | 0.209 | N | 0.325 | neutral | None | None | None | None | N |
| E/T | 0.3207 | likely_benign | 0.2631 | benign | 0.125 | Stabilizing | 0.561 | D | 0.361 | neutral | None | None | None | None | N |
| E/V | 0.4659 | ambiguous | 0.3989 | ambiguous | 0.085 | Stabilizing | 0.326 | N | 0.392 | neutral | N | 0.511416757 | None | None | N |
| E/W | 0.9571 | likely_pathogenic | 0.9391 | pathogenic | 0.025 | Stabilizing | 0.991 | D | 0.42 | neutral | None | None | None | None | N |
| E/Y | 0.7513 | likely_pathogenic | 0.6883 | pathogenic | 0.153 | Stabilizing | 0.965 | D | 0.439 | 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.