Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21414 | 64465;64466;64467 | chr2:178586661;178586660;178586659 | chr2:179451388;179451387;179451386 |
| N2AB | 19773 | 59542;59543;59544 | chr2:178586661;178586660;178586659 | chr2:179451388;179451387;179451386 |
| N2A | 18846 | 56761;56762;56763 | chr2:178586661;178586660;178586659 | chr2:179451388;179451387;179451386 |
| N2B | 12349 | 37270;37271;37272 | chr2:178586661;178586660;178586659 | chr2:179451388;179451387;179451386 |
| Novex-1 | 12474 | 37645;37646;37647 | chr2:178586661;178586660;178586659 | chr2:179451388;179451387;179451386 |
| Novex-2 | 12541 | 37846;37847;37848 | chr2:178586661;178586660;178586659 | chr2:179451388;179451387;179451386 |
| 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/C | rs373478378  |
-0.093 | 0.996 | N | 0.231 | 0.341 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs373478378 |
-0.093 | 0.996 | N | 0.231 | 0.341 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs373478378 |
-0.093 | 0.996 | N | 0.231 | 0.341 | None | gnomAD-4.0.0 | 1.85986E-06 | None | None | None | None | N | None | 1.33608E-05 | 0 | None | 0 | 0 | None | 0 | 1.64636E-04 | 8.47887E-07 | 0 | 0 |
| R/H | rs727504690 |
-0.597 | 0.009 | N | 0.207 | 0.135 | 0.178374595973 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 5.59E-05 | None | 9.8E-05 | None | 0 | 0 | 0 |
| R/H | rs727504690 |
-0.597 | 0.009 | N | 0.207 | 0.135 | 0.178374595973 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78927E-04 |
| R/H | rs727504690 |
-0.597 | 0.009 | N | 0.207 | 0.135 | 0.178374595973 | gnomAD-4.0.0 | 1.11591E-05 | None | None | None | None | N | None | 2.67258E-05 | 1.668E-05 | None | 0 | 2.23374E-05 | None | 0 | 0 | 2.54366E-06 | 1.0981E-04 | 1.6019E-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 | 0.3464 | ambiguous | 0.2453 | benign | -0.117 | Destabilizing | 0.228 | N | 0.379 | neutral | None | None | None | None | N |
| R/C | 0.2111 | likely_benign | 0.1639 | benign | -0.138 | Destabilizing | 0.996 | D | 0.231 | neutral | N | 0.494700652 | None | None | N |
| R/D | 0.5868 | likely_pathogenic | 0.4507 | ambiguous | 0.065 | Stabilizing | 0.129 | N | 0.311 | neutral | None | None | None | None | N |
| R/E | 0.3484 | ambiguous | 0.2604 | benign | 0.161 | Stabilizing | 0.004 | N | 0.228 | neutral | None | None | None | None | N |
| R/F | 0.5647 | likely_pathogenic | 0.4242 | ambiguous | -0.166 | Destabilizing | 0.716 | D | 0.262 | neutral | None | None | None | None | N |
| R/G | 0.2714 | likely_benign | 0.2016 | benign | -0.375 | Destabilizing | 0.221 | N | 0.303 | neutral | N | 0.435209631 | None | None | N |
| R/H | 0.109 | likely_benign | 0.0885 | benign | -0.882 | Destabilizing | 0.009 | N | 0.207 | neutral | N | 0.46591654 | None | None | N |
| R/I | 0.247 | likely_benign | 0.1739 | benign | 0.543 | Stabilizing | 0.836 | D | 0.295 | neutral | None | None | None | None | N |
| R/K | 0.1009 | likely_benign | 0.0887 | benign | -0.123 | Destabilizing | 0.004 | N | 0.187 | neutral | None | None | None | None | N |
| R/L | 0.2382 | likely_benign | 0.1758 | benign | 0.543 | Stabilizing | 0.579 | D | 0.361 | neutral | N | 0.451717879 | None | None | N |
| R/M | 0.2907 | likely_benign | 0.2064 | benign | 0.09 | Stabilizing | 0.94 | D | 0.281 | neutral | None | None | None | None | N |
| R/N | 0.4678 | ambiguous | 0.3438 | ambiguous | 0.215 | Stabilizing | 0.002 | N | 0.249 | neutral | None | None | None | None | N |
| R/P | 0.7755 | likely_pathogenic | 0.689 | pathogenic | 0.346 | Stabilizing | 0.968 | D | 0.331 | neutral | N | 0.46281752 | None | None | N |
| R/Q | 0.1089 | likely_benign | 0.0911 | benign | 0.111 | Stabilizing | 0.418 | N | 0.306 | neutral | None | None | None | None | N |
| R/S | 0.426 | ambiguous | 0.3076 | benign | -0.266 | Destabilizing | 0.221 | N | 0.342 | neutral | N | 0.432804044 | None | None | N |
| R/T | 0.2229 | likely_benign | 0.1525 | benign | -0.009 | Destabilizing | 0.418 | N | 0.34 | neutral | None | None | None | None | N |
| R/V | 0.3008 | likely_benign | 0.2121 | benign | 0.346 | Stabilizing | 0.593 | D | 0.314 | neutral | None | None | None | None | N |
| R/W | 0.2901 | likely_benign | 0.2185 | benign | -0.093 | Destabilizing | 0.983 | D | 0.249 | neutral | None | None | None | None | N |
| R/Y | 0.4192 | ambiguous | 0.3112 | benign | 0.29 | Stabilizing | 0.557 | D | 0.32 | 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.