Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33508 | 100747;100748;100749 | chr2:178536225;178536224;178536223 | chr2:179400952;179400951;179400950 |
| N2AB | 31867 | 95824;95825;95826 | chr2:178536225;178536224;178536223 | chr2:179400952;179400951;179400950 |
| N2A | 30940 | 93043;93044;93045 | chr2:178536225;178536224;178536223 | chr2:179400952;179400951;179400950 |
| N2B | 24443 | 73552;73553;73554 | chr2:178536225;178536224;178536223 | chr2:179400952;179400951;179400950 |
| Novex-1 | 24568 | 73927;73928;73929 | chr2:178536225;178536224;178536223 | chr2:179400952;179400951;179400950 |
| Novex-2 | 24635 | 74128;74129;74130 | chr2:178536225;178536224;178536223 | chr2:179400952;179400951;179400950 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs758673294  |
-0.489 | None | N | 0.245 | 0.117 | 0.315903272564 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/S | None | None | 0.113 | N | 0.433 | 0.24 | 0.141422826196 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| R/T | rs758673294 |
-0.781 | 0.382 | N | 0.463 | 0.263 | 0.37762505005 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/T | rs758673294 |
-0.781 | 0.382 | N | 0.463 | 0.263 | 0.37762505005 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/T | rs758673294 |
-0.781 | 0.382 | N | 0.463 | 0.263 | 0.37762505005 | gnomAD-4.0.0 | 5.12777E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.1836E-06 | 0 | 2.84641E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8075 | likely_pathogenic | 0.8074 | pathogenic | -0.097 | Destabilizing | 0.145 | N | 0.447 | neutral | None | None | None | None | N |
| R/C | 0.5431 | ambiguous | 0.5904 | pathogenic | -0.279 | Destabilizing | 0.985 | D | 0.417 | neutral | None | None | None | None | N |
| R/D | 0.957 | likely_pathogenic | 0.9526 | pathogenic | -0.137 | Destabilizing | 0.45 | N | 0.477 | neutral | None | None | None | None | N |
| R/E | 0.8526 | likely_pathogenic | 0.8552 | pathogenic | -0.087 | Destabilizing | 0.048 | N | 0.379 | neutral | None | None | None | None | N |
| R/F | 0.9256 | likely_pathogenic | 0.9314 | pathogenic | -0.362 | Destabilizing | 0.876 | D | 0.417 | neutral | None | None | None | None | N |
| R/G | 0.7205 | likely_pathogenic | 0.7082 | pathogenic | -0.271 | Destabilizing | 0.382 | N | 0.453 | neutral | N | 0.470682934 | None | None | N |
| R/H | 0.3069 | likely_benign | 0.3148 | benign | -0.657 | Destabilizing | 0.707 | D | 0.371 | neutral | None | None | None | None | N |
| R/I | 0.7337 | likely_pathogenic | 0.7597 | pathogenic | 0.321 | Stabilizing | 0.646 | D | 0.431 | neutral | N | 0.447691431 | None | None | N |
| R/K | 0.1288 | likely_benign | 0.1043 | benign | -0.183 | Destabilizing | None | N | 0.245 | neutral | N | 0.398107973 | None | None | N |
| R/L | 0.6185 | likely_pathogenic | 0.6635 | pathogenic | 0.321 | Stabilizing | 0.254 | N | 0.453 | neutral | None | None | None | None | N |
| R/M | 0.7361 | likely_pathogenic | 0.759 | pathogenic | -0.031 | Destabilizing | 0.88 | D | 0.422 | neutral | None | None | None | None | N |
| R/N | 0.9064 | likely_pathogenic | 0.8902 | pathogenic | 0.034 | Stabilizing | 0.45 | N | 0.371 | neutral | None | None | None | None | N |
| R/P | 0.7547 | likely_pathogenic | 0.7254 | pathogenic | 0.201 | Stabilizing | 0.624 | D | 0.451 | neutral | None | None | None | None | N |
| R/Q | 0.2903 | likely_benign | 0.3003 | benign | -0.093 | Destabilizing | 0.232 | N | 0.379 | neutral | None | None | None | None | N |
| R/S | 0.8728 | likely_pathogenic | 0.8649 | pathogenic | -0.333 | Destabilizing | 0.113 | N | 0.433 | neutral | N | 0.437645009 | None | None | N |
| R/T | 0.7359 | likely_pathogenic | 0.7349 | pathogenic | -0.159 | Destabilizing | 0.382 | N | 0.463 | neutral | N | 0.433626056 | None | None | N |
| R/V | 0.7731 | likely_pathogenic | 0.7923 | pathogenic | 0.201 | Stabilizing | 0.197 | N | 0.475 | neutral | None | None | None | None | N |
| R/W | 0.6845 | likely_pathogenic | 0.7317 | pathogenic | -0.411 | Destabilizing | 0.99 | D | 0.438 | neutral | None | None | None | None | N |
| R/Y | 0.8568 | likely_pathogenic | 0.8632 | pathogenic | -0.009 | Destabilizing | 0.876 | D | 0.437 | 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.