Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26212 | 78859;78860;78861 | chr2:178567498;178567497;178567496 | chr2:179432225;179432224;179432223 |
| N2AB | 24571 | 73936;73937;73938 | chr2:178567498;178567497;178567496 | chr2:179432225;179432224;179432223 |
| N2A | 23644 | 71155;71156;71157 | chr2:178567498;178567497;178567496 | chr2:179432225;179432224;179432223 |
| N2B | 17147 | 51664;51665;51666 | chr2:178567498;178567497;178567496 | chr2:179432225;179432224;179432223 |
| Novex-1 | 17272 | 52039;52040;52041 | chr2:178567498;178567497;178567496 | chr2:179432225;179432224;179432223 |
| Novex-2 | 17339 | 52240;52241;52242 | chr2:178567498;178567497;178567496 | chr2:179432225;179432224;179432223 |
| 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/S | rs756880931  |
-0.619 | 0.001 | N | 0.287 | 0.211 | 0.0954503805726 | gnomAD-4.0.0 | 6.84549E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16104E-05 | 0 |
| R/T | rs11685237 |
None | 0.001 | N | 0.277 | 0.264 | 0.154104182512 | 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/T | rs11685237 |
None | 0.001 | N | 0.277 | 0.264 | 0.154104182512 | gnomAD-4.0.0 | 6.5754E-06 | None | None | None | None | N | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2745 | likely_benign | 0.3171 | benign | -0.59 | Destabilizing | 0.007 | N | 0.375 | neutral | None | None | None | None | N |
| R/C | 0.1088 | likely_benign | 0.1244 | benign | -0.75 | Destabilizing | 0.864 | D | 0.431 | neutral | None | None | None | None | N |
| R/D | 0.6719 | likely_pathogenic | 0.7216 | pathogenic | -0.035 | Destabilizing | 0.038 | N | 0.511 | neutral | None | None | None | None | N |
| R/E | 0.2944 | likely_benign | 0.3399 | benign | 0.12 | Stabilizing | 0.016 | N | 0.455 | neutral | None | None | None | None | N |
| R/F | 0.3617 | ambiguous | 0.4212 | ambiguous | -0.351 | Destabilizing | 0.628 | D | 0.445 | neutral | None | None | None | None | N |
| R/G | 0.269 | likely_benign | 0.3105 | benign | -0.9 | Destabilizing | 0.024 | N | 0.47 | neutral | N | 0.496193038 | None | None | N |
| R/H | 0.0806 | likely_benign | 0.0908 | benign | -1.158 | Destabilizing | 0.356 | N | 0.455 | neutral | None | None | None | None | N |
| R/I | 0.1338 | likely_benign | 0.1606 | benign | 0.243 | Stabilizing | 0.171 | N | 0.499 | neutral | N | 0.495553509 | None | None | N |
| R/K | 0.0719 | likely_benign | 0.0722 | benign | -0.452 | Destabilizing | None | N | 0.189 | neutral | N | 0.426154926 | None | None | N |
| R/L | 0.1435 | likely_benign | 0.1714 | benign | 0.243 | Stabilizing | 0.031 | N | 0.497 | neutral | None | None | None | None | N |
| R/M | 0.1611 | likely_benign | 0.1861 | benign | -0.362 | Destabilizing | 0.628 | D | 0.465 | neutral | None | None | None | None | N |
| R/N | 0.4469 | ambiguous | 0.5054 | ambiguous | -0.348 | Destabilizing | 0.001 | N | 0.197 | neutral | None | None | None | None | N |
| R/P | 0.7825 | likely_pathogenic | 0.8265 | pathogenic | -0.014 | Destabilizing | 0.136 | N | 0.505 | neutral | None | None | None | None | N |
| R/Q | 0.0859 | likely_benign | 0.0917 | benign | -0.346 | Destabilizing | 0.038 | N | 0.397 | neutral | None | None | None | None | N |
| R/S | 0.3029 | likely_benign | 0.3533 | ambiguous | -0.991 | Destabilizing | 0.001 | N | 0.287 | neutral | N | 0.452802809 | None | None | N |
| R/T | 0.1217 | likely_benign | 0.1479 | benign | -0.641 | Destabilizing | 0.001 | N | 0.277 | neutral | N | 0.422746474 | None | None | N |
| R/V | 0.1708 | likely_benign | 0.192 | benign | -0.014 | Destabilizing | 0.072 | N | 0.503 | neutral | None | None | None | None | N |
| R/W | 0.1475 | likely_benign | 0.1663 | benign | -0.125 | Destabilizing | 0.864 | D | 0.45 | neutral | None | None | None | None | N |
| R/Y | 0.2777 | likely_benign | 0.3221 | benign | 0.177 | Stabilizing | 0.628 | D | 0.444 | 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.