Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14791 | 44596;44597;44598 | chr2:178629354;178629353;178629352 | chr2:179494081;179494080;179494079 |
| N2AB | 13150 | 39673;39674;39675 | chr2:178629354;178629353;178629352 | chr2:179494081;179494080;179494079 |
| N2A | 12223 | 36892;36893;36894 | chr2:178629354;178629353;178629352 | chr2:179494081;179494080;179494079 |
| N2B | 5726 | 17401;17402;17403 | chr2:178629354;178629353;178629352 | chr2:179494081;179494080;179494079 |
| Novex-1 | 5851 | 17776;17777;17778 | chr2:178629354;178629353;178629352 | chr2:179494081;179494080;179494079 |
| Novex-2 | 5918 | 17977;17978;17979 | chr2:178629354;178629353;178629352 | chr2:179494081;179494080;179494079 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs772552324  |
0.106 | 0.946 | N | 0.475 | 0.226 | 0.294918367191 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/E | rs772552324 |
0.106 | 0.946 | N | 0.475 | 0.226 | 0.294918367191 | gnomAD-4.0.0 | 6.84602E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15972E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2638 | likely_benign | 0.2935 | benign | -0.192 | Destabilizing | 0.811 | D | 0.616 | neutral | D | 0.541225595 | None | None | N |
| D/C | 0.8021 | likely_pathogenic | 0.8157 | pathogenic | -0.132 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| D/E | 0.2779 | likely_benign | 0.293 | benign | -0.294 | Destabilizing | 0.946 | D | 0.475 | neutral | N | 0.506019939 | None | None | N |
| D/F | 0.7396 | likely_pathogenic | 0.7563 | pathogenic | -0.085 | Destabilizing | 0.996 | D | 0.655 | neutral | None | None | None | None | N |
| D/G | 0.1292 | likely_benign | 0.1226 | benign | -0.383 | Destabilizing | 0.004 | N | 0.348 | neutral | N | 0.48065576 | None | None | N |
| D/H | 0.4251 | ambiguous | 0.4691 | ambiguous | 0.226 | Stabilizing | 0.999 | D | 0.541 | neutral | D | 0.595878374 | None | None | N |
| D/I | 0.5977 | likely_pathogenic | 0.6535 | pathogenic | 0.262 | Stabilizing | 0.996 | D | 0.662 | neutral | None | None | None | None | N |
| D/K | 0.5666 | likely_pathogenic | 0.6007 | pathogenic | 0.223 | Stabilizing | 0.988 | D | 0.513 | neutral | None | None | None | None | N |
| D/L | 0.5971 | likely_pathogenic | 0.6198 | pathogenic | 0.262 | Stabilizing | 0.988 | D | 0.653 | neutral | None | None | None | None | N |
| D/M | 0.7812 | likely_pathogenic | 0.8003 | pathogenic | 0.207 | Stabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/N | 0.1178 | likely_benign | 0.1315 | benign | -0.04 | Destabilizing | 0.896 | D | 0.541 | neutral | N | 0.511986766 | None | None | N |
| D/P | 0.8464 | likely_pathogenic | 0.863 | pathogenic | 0.132 | Stabilizing | 0.996 | D | 0.545 | neutral | None | None | None | None | N |
| D/Q | 0.5403 | ambiguous | 0.5679 | pathogenic | -0.001 | Destabilizing | 0.996 | D | 0.495 | neutral | None | None | None | None | N |
| D/R | 0.6036 | likely_pathogenic | 0.6346 | pathogenic | 0.487 | Stabilizing | 0.988 | D | 0.63 | neutral | None | None | None | None | N |
| D/S | 0.2176 | likely_benign | 0.2349 | benign | -0.167 | Destabilizing | 0.919 | D | 0.506 | neutral | None | None | None | None | N |
| D/T | 0.3979 | ambiguous | 0.4404 | ambiguous | -0.016 | Destabilizing | 0.988 | D | 0.513 | neutral | None | None | None | None | N |
| D/V | 0.399 | ambiguous | 0.4516 | ambiguous | 0.132 | Stabilizing | 0.984 | D | 0.653 | neutral | D | 0.563998598 | None | None | N |
| D/W | 0.9276 | likely_pathogenic | 0.9357 | pathogenic | 0.039 | Stabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2976 | likely_benign | 0.3296 | benign | 0.153 | Stabilizing | 0.995 | D | 0.659 | neutral | D | 0.661053303 | 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.