Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9421 | 28486;28487;28488 | chr2:178710836;178710835;178710834 | chr2:179575563;179575562;179575561 |
| N2AB | 9104 | 27535;27536;27537 | chr2:178710836;178710835;178710834 | chr2:179575563;179575562;179575561 |
| N2A | 8177 | 24754;24755;24756 | chr2:178710836;178710835;178710834 | chr2:179575563;179575562;179575561 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/M | rs375209383  |
0.173 | 0.161 | None | 0.373 | 0.382 | None | gnomAD-2.1.1 | 8.56E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.09878E-04 | None | 1.96066E-04 | None | 7.99E-05 | 6.25E-05 | 0 |
| T/M | rs375209383 |
0.173 | 0.161 | None | 0.373 | 0.382 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 3.85951E-04 | None | 9.43E-05 | 0 | 4.41E-05 | 0 | 0 |
| T/M | rs375209383 |
0.173 | 0.161 | None | 0.373 | 0.382 | None | gnomAD-4.0.0 | 7.18783E-05 | None | None | None | None | I | None | 2.66624E-05 | 0 | None | 0 | 7.57778E-04 | None | 3.1248E-05 | 1.64962E-04 | 4.23793E-05 | 2.52531E-04 | 6.40205E-05 |
| T/S | None | None | 0.006 | None | 0.215 | 0.191 | 0.193865811164 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1434 | likely_benign | 0.1377 | benign | -0.911 | Destabilizing | 0.09 | N | 0.404 | neutral | None | None | None | None | I |
| T/C | 0.7338 | likely_pathogenic | 0.7647 | pathogenic | -0.426 | Destabilizing | 0.981 | D | 0.364 | neutral | None | None | None | None | I |
| T/D | 0.6374 | likely_pathogenic | 0.6648 | pathogenic | -0.286 | Destabilizing | 0.388 | N | 0.368 | neutral | None | None | None | None | I |
| T/E | 0.4989 | ambiguous | 0.4928 | ambiguous | -0.232 | Destabilizing | 0.388 | N | 0.388 | neutral | None | None | None | None | I |
| T/F | 0.4344 | ambiguous | 0.4039 | ambiguous | -0.724 | Destabilizing | 0.69 | D | 0.436 | neutral | None | None | None | None | I |
| T/G | 0.3988 | ambiguous | 0.4283 | ambiguous | -1.233 | Destabilizing | 0.241 | N | 0.406 | neutral | None | None | None | None | I |
| T/H | 0.4326 | ambiguous | 0.4225 | ambiguous | -1.383 | Destabilizing | 0.981 | D | 0.401 | neutral | None | None | None | None | I |
| T/I | 0.4038 | ambiguous | 0.344 | ambiguous | -0.125 | Destabilizing | 0.527 | D | 0.385 | neutral | None | None | None | None | I |
| T/K | 0.3152 | likely_benign | 0.3005 | benign | -0.752 | Destabilizing | 0.016 | N | 0.227 | neutral | None | None | None | None | I |
| T/L | 0.2322 | likely_benign | 0.1864 | benign | -0.125 | Destabilizing | 0.098 | N | 0.383 | neutral | None | None | None | None | I |
| T/M | 0.1554 | likely_benign | 0.1246 | benign | 0.093 | Stabilizing | 0.161 | N | 0.373 | neutral | None | None | None | None | I |
| T/N | 0.2542 | likely_benign | 0.264 | benign | -0.787 | Destabilizing | 0.388 | N | 0.387 | neutral | None | None | None | None | I |
| T/P | 0.6892 | likely_pathogenic | 0.6912 | pathogenic | -0.354 | Destabilizing | 0.001 | N | 0.232 | neutral | None | None | None | None | I |
| T/Q | 0.3576 | ambiguous | 0.3308 | benign | -0.823 | Destabilizing | 0.69 | D | 0.398 | neutral | None | None | None | None | I |
| T/R | 0.2352 | likely_benign | 0.1978 | benign | -0.604 | Destabilizing | 0.681 | D | 0.381 | neutral | None | None | None | None | I |
| T/S | 0.1338 | likely_benign | 0.1492 | benign | -1.092 | Destabilizing | 0.006 | N | 0.215 | neutral | None | None | None | None | I |
| T/V | 0.3169 | likely_benign | 0.278 | benign | -0.354 | Destabilizing | 0.241 | N | 0.338 | neutral | None | None | None | None | I |
| T/W | 0.731 | likely_pathogenic | 0.7243 | pathogenic | -0.704 | Destabilizing | 0.981 | D | 0.519 | neutral | None | None | None | None | I |
| T/Y | 0.4718 | ambiguous | 0.5094 | ambiguous | -0.477 | Destabilizing | 0.818 | D | 0.421 | 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.