Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8280 | 25063;25064;25065 | chr2:178718168;178718167;178718166 | chr2:179582895;179582894;179582893 |
| N2AB | 7963 | 24112;24113;24114 | chr2:178718168;178718167;178718166 | chr2:179582895;179582894;179582893 |
| N2A | 7036 | 21331;21332;21333 | chr2:178718168;178718167;178718166 | chr2:179582895;179582894;179582893 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs375219172  |
-0.294 | 0.44 | N | 0.457 | 0.335 | None | gnomAD-2.1.1 | 8.23E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| P/L | rs375219172 |
-0.294 | 0.44 | N | 0.457 | 0.335 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/L | rs375219172 |
-0.294 | 0.44 | N | 0.457 | 0.335 | None | gnomAD-4.0.0 | 8.09428E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10216E-05 | 0 | 0 |
| P/R | rs375219172 |
None | 0.734 | N | 0.463 | 0.384 | 0.518752145996 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/R | rs375219172 |
None | 0.734 | N | 0.463 | 0.384 | 0.518752145996 | gnomAD-4.0.0 | 1.86791E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54345E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0713 | likely_benign | 0.0703 | benign | -0.855 | Destabilizing | 0.013 | N | 0.394 | neutral | N | 0.453537181 | None | None | I |
| P/C | 0.5643 | likely_pathogenic | 0.6295 | pathogenic | -0.61 | Destabilizing | 0.001 | N | 0.367 | neutral | None | None | None | None | I |
| P/D | 0.3747 | ambiguous | 0.4283 | ambiguous | -0.638 | Destabilizing | None | N | 0.225 | neutral | None | None | None | None | I |
| P/E | 0.252 | likely_benign | 0.274 | benign | -0.738 | Destabilizing | 0.007 | N | 0.373 | neutral | None | None | None | None | I |
| P/F | 0.4062 | ambiguous | 0.4482 | ambiguous | -0.923 | Destabilizing | 0.881 | D | 0.468 | neutral | None | None | None | None | I |
| P/G | 0.283 | likely_benign | 0.3167 | benign | -1.044 | Destabilizing | 0.042 | N | 0.373 | neutral | None | None | None | None | I |
| P/H | 0.1712 | likely_benign | 0.1969 | benign | -0.56 | Destabilizing | 0.676 | D | 0.408 | neutral | N | 0.506448946 | None | None | I |
| P/I | 0.2831 | likely_benign | 0.2992 | benign | -0.489 | Destabilizing | 0.785 | D | 0.489 | neutral | None | None | None | None | I |
| P/K | 0.2553 | likely_benign | 0.287 | benign | -0.672 | Destabilizing | 0.343 | N | 0.377 | neutral | None | None | None | None | I |
| P/L | 0.1175 | likely_benign | 0.1265 | benign | -0.489 | Destabilizing | 0.44 | N | 0.457 | neutral | N | 0.499637617 | None | None | I |
| P/M | 0.269 | likely_benign | 0.271 | benign | -0.328 | Destabilizing | 0.894 | D | 0.409 | neutral | None | None | None | None | I |
| P/N | 0.246 | likely_benign | 0.2705 | benign | -0.343 | Destabilizing | 0.061 | N | 0.393 | neutral | None | None | None | None | I |
| P/Q | 0.1415 | likely_benign | 0.1521 | benign | -0.635 | Destabilizing | 0.015 | N | 0.23 | neutral | None | None | None | None | I |
| P/R | 0.1633 | likely_benign | 0.1933 | benign | -0.074 | Destabilizing | 0.734 | D | 0.463 | neutral | N | 0.473624452 | None | None | I |
| P/S | 0.102 | likely_benign | 0.1031 | benign | -0.755 | Destabilizing | None | N | 0.155 | neutral | N | 0.380460787 | None | None | I |
| P/T | 0.0858 | likely_benign | 0.0845 | benign | -0.759 | Destabilizing | 0.02 | N | 0.38 | neutral | N | 0.411111768 | None | None | I |
| P/V | 0.1948 | likely_benign | 0.2025 | benign | -0.575 | Destabilizing | 0.154 | N | 0.397 | neutral | None | None | None | None | I |
| P/W | 0.5786 | likely_pathogenic | 0.6608 | pathogenic | -0.991 | Destabilizing | 0.988 | D | 0.511 | neutral | None | None | None | None | I |
| P/Y | 0.3622 | ambiguous | 0.4159 | ambiguous | -0.711 | Destabilizing | 0.881 | D | 0.473 | 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.