Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18362 | 55309;55310;55311 | chr2:178602318;178602317;178602316 | chr2:179467045;179467044;179467043 |
| N2AB | 16721 | 50386;50387;50388 | chr2:178602318;178602317;178602316 | chr2:179467045;179467044;179467043 |
| N2A | 15794 | 47605;47606;47607 | chr2:178602318;178602317;178602316 | chr2:179467045;179467044;179467043 |
| N2B | 9297 | 28114;28115;28116 | chr2:178602318;178602317;178602316 | chr2:179467045;179467044;179467043 |
| Novex-1 | 9422 | 28489;28490;28491 | chr2:178602318;178602317;178602316 | chr2:179467045;179467044;179467043 |
| Novex-2 | 9489 | 28690;28691;28692 | chr2:178602318;178602317;178602316 | chr2:179467045;179467044;179467043 |
| 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/H | rs1467267606  |
-0.237 | 0.412 | N | 0.339 | 0.141 | 0.188950314367 | 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/H | rs1467267606 |
-0.237 | 0.412 | N | 0.339 | 0.141 | 0.188950314367 | gnomAD-4.0.0 | 1.36916E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31986E-05 | 0 |
| D/N | None | None | 0.047 | N | 0.227 | 0.099 | 0.158396225186 | gnomAD-4.0.0 | 6.84578E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99798E-07 | 0 | 0 |
| D/Y | None | None | 0.412 | N | 0.441 | 0.191 | 0.383089235449 | gnomAD-4.0.0 | 1.36916E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7996E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.0959 | likely_benign | 0.1093 | benign | -0.215 | Destabilizing | 0.009 | N | 0.241 | neutral | N | 0.470543208 | None | None | N |
| D/C | 0.364 | ambiguous | 0.4211 | ambiguous | 0.275 | Stabilizing | 0.914 | D | 0.31 | neutral | None | None | None | None | N |
| D/E | 0.1051 | likely_benign | 0.1157 | benign | -0.216 | Destabilizing | 0.039 | N | 0.219 | neutral | N | 0.406990375 | None | None | N |
| D/F | 0.293 | likely_benign | 0.329 | benign | -0.332 | Destabilizing | 0.314 | N | 0.482 | neutral | None | None | None | None | N |
| D/G | 0.1221 | likely_benign | 0.1382 | benign | -0.375 | Destabilizing | None | N | 0.155 | neutral | N | 0.48793689 | None | None | N |
| D/H | 0.1958 | likely_benign | 0.2255 | benign | -0.244 | Destabilizing | 0.412 | N | 0.339 | neutral | N | 0.455758247 | None | None | N |
| D/I | 0.1627 | likely_benign | 0.1881 | benign | 0.148 | Stabilizing | 0.061 | N | 0.523 | neutral | None | None | None | None | N |
| D/K | 0.2149 | likely_benign | 0.237 | benign | 0.535 | Stabilizing | 0.061 | N | 0.379 | neutral | None | None | None | None | N |
| D/L | 0.1585 | likely_benign | 0.1911 | benign | 0.148 | Stabilizing | None | N | 0.323 | neutral | None | None | None | None | N |
| D/M | 0.3128 | likely_benign | 0.3537 | ambiguous | 0.381 | Stabilizing | 0.314 | N | 0.351 | neutral | None | None | None | None | N |
| D/N | 0.0895 | likely_benign | 0.0938 | benign | 0.309 | Stabilizing | 0.047 | N | 0.227 | neutral | N | 0.488590251 | None | None | N |
| D/P | 0.2594 | likely_benign | 0.3134 | benign | 0.048 | Stabilizing | None | N | 0.144 | neutral | None | None | None | None | N |
| D/Q | 0.1922 | likely_benign | 0.2246 | benign | 0.315 | Stabilizing | 0.116 | N | 0.308 | neutral | None | None | None | None | N |
| D/R | 0.2443 | likely_benign | 0.272 | benign | 0.541 | Stabilizing | 0.116 | N | 0.568 | neutral | None | None | None | None | N |
| D/S | 0.0956 | likely_benign | 0.1059 | benign | 0.221 | Stabilizing | 0.001 | N | 0.109 | neutral | None | None | None | None | N |
| D/T | 0.1432 | likely_benign | 0.1624 | benign | 0.347 | Stabilizing | 0.026 | N | 0.281 | neutral | None | None | None | None | N |
| D/V | 0.1096 | likely_benign | 0.1245 | benign | 0.048 | Stabilizing | 0.047 | N | 0.413 | neutral | N | 0.481992353 | None | None | N |
| D/W | 0.6752 | likely_pathogenic | 0.7122 | pathogenic | -0.254 | Destabilizing | 0.914 | D | 0.404 | neutral | None | None | None | None | N |
| D/Y | 0.1345 | likely_benign | 0.1464 | benign | -0.102 | Destabilizing | 0.412 | N | 0.441 | neutral | N | 0.461443013 | 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.