Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19432 | 58519;58520;58521 | chr2:178594099;178594098;178594097 | chr2:179458826;179458825;179458824 |
| N2AB | 17791 | 53596;53597;53598 | chr2:178594099;178594098;178594097 | chr2:179458826;179458825;179458824 |
| N2A | 16864 | 50815;50816;50817 | chr2:178594099;178594098;178594097 | chr2:179458826;179458825;179458824 |
| N2B | 10367 | 31324;31325;31326 | chr2:178594099;178594098;178594097 | chr2:179458826;179458825;179458824 |
| Novex-1 | 10492 | 31699;31700;31701 | chr2:178594099;178594098;178594097 | chr2:179458826;179458825;179458824 |
| Novex-2 | 10559 | 31900;31901;31902 | chr2:178594099;178594098;178594097 | chr2:179458826;179458825;179458824 |
| 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 | rs1345945391  |
-0.037 | 0.022 | N | 0.257 | 0.275 | 0.216624796971 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87853E-04 | 0 | 0 |
| R/C | rs1345945391 |
-0.037 | 0.022 | N | 0.257 | 0.275 | 0.216624796971 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 0 | 0 | 0 |
| R/C | rs1345945391 |
-0.037 | 0.022 | N | 0.257 | 0.275 | 0.216624796971 | gnomAD-4.0.0 | 3.71919E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.5626E-05 | 0 | 3.39093E-06 | 0 | 1.60169E-05 |
| R/H | rs745631866 |
-1.09 | 0.956 | N | 0.259 | 0.308 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 8.71E-05 | None | 0 | 5.61E-05 | None | 9.8E-05 | None | 0 | 0 | 0 |
| R/H | rs745631866 |
-1.09 | 0.956 | N | 0.259 | 0.308 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 1.47E-05 | 0 | 4.78927E-04 |
| R/H | rs745631866 |
-1.09 | 0.956 | N | 0.259 | 0.308 | None | gnomAD-4.0.0 | 1.48771E-05 | None | None | None | None | N | None | 1.33604E-05 | 8.34251E-05 | None | 0 | 1.11772E-04 | None | 0 | 0 | 5.08644E-06 | 4.39203E-05 | 4.80492E-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 | 0.3797 | ambiguous | 0.3363 | benign | -0.828 | Destabilizing | 0.129 | N | 0.274 | neutral | None | None | None | None | N |
| R/C | 0.1348 | likely_benign | 0.1265 | benign | -0.69 | Destabilizing | 0.022 | N | 0.257 | neutral | N | 0.508494985 | None | None | N |
| R/D | 0.4794 | ambiguous | 0.4626 | ambiguous | -0.23 | Destabilizing | 0.001 | N | 0.222 | neutral | None | None | None | None | N |
| R/E | 0.287 | likely_benign | 0.2584 | benign | -0.096 | Destabilizing | 0.004 | N | 0.155 | neutral | None | None | None | None | N |
| R/F | 0.5203 | ambiguous | 0.4945 | ambiguous | -0.599 | Destabilizing | 0.836 | D | 0.327 | neutral | None | None | None | None | N |
| R/G | 0.2402 | likely_benign | 0.2153 | benign | -1.166 | Destabilizing | 0.362 | N | 0.3 | neutral | N | 0.480222513 | None | None | N |
| R/H | 0.0919 | likely_benign | 0.0942 | benign | -1.468 | Destabilizing | 0.956 | D | 0.259 | neutral | N | 0.482053855 | None | None | N |
| R/I | 0.2551 | likely_benign | 0.2216 | benign | 0.091 | Stabilizing | 0.716 | D | 0.37 | neutral | None | None | None | None | N |
| R/K | 0.1407 | likely_benign | 0.134 | benign | -0.935 | Destabilizing | 0.129 | N | 0.268 | neutral | None | None | None | None | N |
| R/L | 0.2632 | likely_benign | 0.2326 | benign | 0.091 | Stabilizing | 0.408 | N | 0.298 | neutral | N | 0.484514927 | None | None | N |
| R/M | 0.2836 | likely_benign | 0.2529 | benign | -0.158 | Destabilizing | 0.94 | D | 0.294 | neutral | None | None | None | None | N |
| R/N | 0.39 | ambiguous | 0.3942 | ambiguous | -0.397 | Destabilizing | 0.418 | N | 0.216 | neutral | None | None | None | None | N |
| R/P | 0.8844 | likely_pathogenic | 0.8591 | pathogenic | -0.194 | Destabilizing | 0.895 | D | 0.345 | neutral | N | 0.489883751 | None | None | N |
| R/Q | 0.0912 | likely_benign | 0.0863 | benign | -0.52 | Destabilizing | 0.027 | N | 0.175 | neutral | None | None | None | None | N |
| R/S | 0.3844 | ambiguous | 0.3506 | ambiguous | -1.125 | Destabilizing | 0.362 | N | 0.285 | neutral | N | 0.472740548 | None | None | N |
| R/T | 0.1972 | likely_benign | 0.1698 | benign | -0.802 | Destabilizing | 0.418 | N | 0.296 | neutral | None | None | None | None | N |
| R/V | 0.3375 | likely_benign | 0.3101 | benign | -0.194 | Destabilizing | 0.264 | N | 0.361 | neutral | None | None | None | None | N |
| R/W | 0.2151 | likely_benign | 0.2029 | benign | -0.251 | Destabilizing | 0.983 | D | 0.317 | neutral | None | None | None | None | N |
| R/Y | 0.3427 | ambiguous | 0.3396 | benign | 0.044 | Stabilizing | 0.94 | D | 0.299 | 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.