Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9523 | 28792;28793;28794 | chr2:178709752;178709751;178709750 | chr2:179574479;179574478;179574477 |
| N2AB | 9206 | 27841;27842;27843 | chr2:178709752;178709751;178709750 | chr2:179574479;179574478;179574477 |
| N2A | 8279 | 25060;25061;25062 | chr2:178709752;178709751;178709750 | chr2:179574479;179574478;179574477 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs775239068  |
-1.144 | None | None | 0.113 | 0.143 | 0.307966526162 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| I/T | rs2076388321 |
None | 0.175 | None | 0.574 | 0.278 | 0.670275282232 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs2076388321 |
None | 0.175 | None | 0.574 | 0.278 | 0.670275282232 | gnomAD-4.0.0 | 6.40462E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19635E-05 | 0 | 0 |
| I/V | rs775239068 |
None | None | None | 0.147 | 0.074 | 0.504604281553 | gnomAD-4.0.0 | 1.59108E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76644E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7626 | likely_pathogenic | 0.7305 | pathogenic | -2.228 | Highly Destabilizing | 0.055 | N | 0.549 | neutral | None | None | None | None | N |
| I/C | 0.9084 | likely_pathogenic | 0.8909 | pathogenic | -1.7 | Destabilizing | 0.883 | D | 0.66 | neutral | None | None | None | None | N |
| I/D | 0.9873 | likely_pathogenic | 0.9892 | pathogenic | -1.363 | Destabilizing | 0.859 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/E | 0.9695 | likely_pathogenic | 0.9739 | pathogenic | -1.237 | Destabilizing | 0.667 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/F | 0.4371 | ambiguous | 0.4278 | ambiguous | -1.39 | Destabilizing | 0.001 | N | 0.359 | neutral | None | None | None | None | N |
| I/G | 0.9617 | likely_pathogenic | 0.9575 | pathogenic | -2.69 | Highly Destabilizing | 0.364 | N | 0.725 | prob.delet. | None | None | None | None | N |
| I/H | 0.9574 | likely_pathogenic | 0.9601 | pathogenic | -1.85 | Destabilizing | 0.958 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/K | 0.9263 | likely_pathogenic | 0.9417 | pathogenic | -1.505 | Destabilizing | 0.602 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/L | 0.1121 | likely_benign | 0.1156 | benign | -0.959 | Destabilizing | None | N | 0.113 | neutral | None | None | None | None | N |
| I/M | 0.1288 | likely_benign | 0.132 | benign | -0.937 | Destabilizing | 0.019 | N | 0.373 | neutral | None | None | None | None | N |
| I/N | 0.8518 | likely_pathogenic | 0.8706 | pathogenic | -1.508 | Destabilizing | 0.859 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/P | 0.9194 | likely_pathogenic | 0.9086 | pathogenic | -1.355 | Destabilizing | 0.859 | D | 0.724 | prob.delet. | None | None | None | None | N |
| I/Q | 0.9247 | likely_pathogenic | 0.9326 | pathogenic | -1.51 | Destabilizing | 0.667 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/R | 0.8973 | likely_pathogenic | 0.9199 | pathogenic | -1.097 | Destabilizing | 0.602 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/S | 0.8505 | likely_pathogenic | 0.8488 | pathogenic | -2.357 | Highly Destabilizing | 0.22 | N | 0.663 | neutral | None | None | None | None | N |
| I/T | 0.7851 | likely_pathogenic | 0.7693 | pathogenic | -2.083 | Highly Destabilizing | 0.175 | N | 0.574 | neutral | None | None | None | None | N |
| I/V | 0.0839 | likely_benign | 0.0761 | benign | -1.355 | Destabilizing | None | N | 0.147 | neutral | None | None | None | None | N |
| I/W | 0.9745 | likely_pathogenic | 0.9742 | pathogenic | -1.495 | Destabilizing | 0.958 | D | 0.672 | neutral | None | None | None | None | N |
| I/Y | 0.8913 | likely_pathogenic | 0.9027 | pathogenic | -1.271 | Destabilizing | 0.331 | N | 0.697 | prob.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.