Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15330 | 46213;46214;46215 | chr2:178620533;178620532;178620531 | chr2:179485260;179485259;179485258 |
| N2AB | 13689 | 41290;41291;41292 | chr2:178620533;178620532;178620531 | chr2:179485260;179485259;179485258 |
| N2A | 12762 | 38509;38510;38511 | chr2:178620533;178620532;178620531 | chr2:179485260;179485259;179485258 |
| N2B | 6265 | 19018;19019;19020 | chr2:178620533;178620532;178620531 | chr2:179485260;179485259;179485258 |
| Novex-1 | 6390 | 19393;19394;19395 | chr2:178620533;178620532;178620531 | chr2:179485260;179485259;179485258 |
| Novex-2 | 6457 | 19594;19595;19596 | chr2:178620533;178620532;178620531 | chr2:179485260;179485259;179485258 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs1476334999  |
-0.45 | 0.517 | N | 0.524 | 0.23 | 0.56468994859 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| V/I | rs1476334999 |
-0.45 | 0.517 | N | 0.524 | 0.23 | 0.56468994859 | gnomAD-4.0.0 | 6.37849E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72803E-06 | 2.86878E-05 | 0 |
| V/L | rs1476334999 |
None | 0.349 | N | 0.435 | 0.268 | 0.423480098753 | gnomAD-4.0.0 | 1.59462E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78443E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.203 | likely_benign | 0.2028 | benign | -1.597 | Destabilizing | 0.001 | N | 0.139 | neutral | N | 0.426659895 | None | None | N |
| V/C | 0.7541 | likely_pathogenic | 0.7683 | pathogenic | -1.001 | Destabilizing | 0.989 | D | 0.586 | neutral | None | None | None | None | N |
| V/D | 0.6427 | likely_pathogenic | 0.5682 | pathogenic | -1.462 | Destabilizing | 0.961 | D | 0.671 | neutral | None | None | None | None | N |
| V/E | 0.5175 | ambiguous | 0.4432 | ambiguous | -1.42 | Destabilizing | 0.901 | D | 0.573 | neutral | D | 0.583073558 | None | None | N |
| V/F | 0.3958 | ambiguous | 0.3208 | benign | -1.198 | Destabilizing | 0.961 | D | 0.607 | neutral | None | None | None | None | N |
| V/G | 0.4004 | ambiguous | 0.3538 | ambiguous | -1.943 | Destabilizing | 0.565 | D | 0.542 | neutral | N | 0.512590353 | None | None | N |
| V/H | 0.7962 | likely_pathogenic | 0.7772 | pathogenic | -1.387 | Destabilizing | 0.996 | D | 0.688 | prob.neutral | None | None | None | None | N |
| V/I | 0.1318 | likely_benign | 0.1092 | benign | -0.722 | Destabilizing | 0.517 | D | 0.524 | neutral | N | 0.509108543 | None | None | N |
| V/K | 0.5847 | likely_pathogenic | 0.5419 | ambiguous | -1.31 | Destabilizing | 0.923 | D | 0.581 | neutral | None | None | None | None | N |
| V/L | 0.4387 | ambiguous | 0.3732 | ambiguous | -0.722 | Destabilizing | 0.349 | N | 0.435 | neutral | N | 0.501476366 | None | None | N |
| V/M | 0.2663 | likely_benign | 0.2184 | benign | -0.601 | Destabilizing | 0.987 | D | 0.503 | neutral | None | None | None | None | N |
| V/N | 0.5468 | ambiguous | 0.4822 | ambiguous | -1.142 | Destabilizing | 0.961 | D | 0.705 | prob.neutral | None | None | None | None | N |
| V/P | 0.9133 | likely_pathogenic | 0.893 | pathogenic | -0.981 | Destabilizing | 0.961 | D | 0.623 | neutral | None | None | None | None | N |
| V/Q | 0.5418 | ambiguous | 0.4911 | ambiguous | -1.245 | Destabilizing | 0.961 | D | 0.668 | neutral | None | None | None | None | N |
| V/R | 0.5379 | ambiguous | 0.5187 | ambiguous | -0.842 | Destabilizing | 0.923 | D | 0.69 | prob.neutral | None | None | None | None | N |
| V/S | 0.3499 | ambiguous | 0.3217 | benign | -1.653 | Destabilizing | 0.633 | D | 0.513 | neutral | None | None | None | None | N |
| V/T | 0.247 | likely_benign | 0.2248 | benign | -1.486 | Destabilizing | 0.775 | D | 0.451 | neutral | None | None | None | None | N |
| V/W | 0.9521 | likely_pathogenic | 0.9339 | pathogenic | -1.393 | Destabilizing | 0.996 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/Y | 0.7564 | likely_pathogenic | 0.7354 | pathogenic | -1.101 | Destabilizing | 0.987 | D | 0.605 | 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.