Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9510 | 28753;28754;28755 | chr2:178709791;178709790;178709789 | chr2:179574518;179574517;179574516 |
| N2AB | 9193 | 27802;27803;27804 | chr2:178709791;178709790;178709789 | chr2:179574518;179574517;179574516 |
| N2A | 8266 | 25021;25022;25023 | chr2:178709791;178709790;178709789 | chr2:179574518;179574517;179574516 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/T | rs2076392914  |
None | 0.007 | None | 0.1 | 0.073 | 0.0806252709748 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| S/T | rs2076392914 |
None | 0.007 | None | 0.1 | 0.073 | 0.0806252709748 | gnomAD-4.0.0 | 6.56996E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| S/Y | rs753125248 |
-0.679 | 0.921 | None | 0.394 | 0.277 | 0.37762505005 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| S/Y | rs753125248 |
-0.679 | 0.921 | None | 0.394 | 0.277 | 0.37762505005 | gnomAD-4.0.0 | 1.16329E-05 | None | None | None | None | N | None | 0 | 2.23644E-05 | None | 0 | 0 | None | 0 | 8.67453E-04 | 0 | 1.27536E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0738 | likely_benign | 0.0649 | benign | -0.609 | Destabilizing | 0.001 | N | 0.089 | neutral | None | None | None | None | N |
| S/C | 0.1125 | likely_benign | 0.1036 | benign | -0.382 | Destabilizing | 0.794 | D | 0.345 | neutral | None | None | None | None | N |
| S/D | 0.393 | ambiguous | 0.2845 | benign | 0.014 | Stabilizing | 0.264 | N | 0.189 | neutral | None | None | None | None | N |
| S/E | 0.5182 | ambiguous | 0.4079 | ambiguous | -0.01 | Destabilizing | 0.002 | N | 0.142 | neutral | None | None | None | None | N |
| S/F | 0.1675 | likely_benign | 0.1407 | benign | -0.871 | Destabilizing | 0.655 | D | 0.435 | neutral | None | None | None | None | N |
| S/G | 0.1166 | likely_benign | 0.0998 | benign | -0.834 | Destabilizing | 0.129 | N | 0.216 | neutral | None | None | None | None | N |
| S/H | 0.3035 | likely_benign | 0.2445 | benign | -1.28 | Destabilizing | 0.836 | D | 0.347 | neutral | None | None | None | None | N |
| S/I | 0.1224 | likely_benign | 0.1046 | benign | -0.129 | Destabilizing | 0.129 | N | 0.383 | neutral | None | None | None | None | N |
| S/K | 0.6815 | likely_pathogenic | 0.5348 | ambiguous | -0.622 | Destabilizing | 0.264 | N | 0.203 | neutral | None | None | None | None | N |
| S/L | 0.0866 | likely_benign | 0.0775 | benign | -0.129 | Destabilizing | 0.001 | N | 0.164 | neutral | None | None | None | None | N |
| S/M | 0.1941 | likely_benign | 0.1776 | benign | 0.08 | Stabilizing | 0.716 | D | 0.361 | neutral | None | None | None | None | N |
| S/N | 0.1428 | likely_benign | 0.1175 | benign | -0.486 | Destabilizing | 0.418 | N | 0.206 | neutral | None | None | None | None | N |
| S/P | 0.1071 | likely_benign | 0.077 | benign | -0.255 | Destabilizing | 0.002 | N | 0.205 | neutral | None | None | None | None | N |
| S/Q | 0.4638 | ambiguous | 0.3711 | ambiguous | -0.633 | Destabilizing | 0.264 | N | 0.297 | neutral | None | None | None | None | N |
| S/R | 0.5462 | ambiguous | 0.4013 | ambiguous | -0.483 | Destabilizing | 0.418 | N | 0.398 | neutral | None | None | None | None | N |
| S/T | 0.0775 | likely_benign | 0.0716 | benign | -0.532 | Destabilizing | 0.007 | N | 0.1 | neutral | None | None | None | None | N |
| S/V | 0.1332 | likely_benign | 0.115 | benign | -0.255 | Destabilizing | 0.01 | N | 0.245 | neutral | None | None | None | None | N |
| S/W | 0.3185 | likely_benign | 0.2655 | benign | -0.86 | Destabilizing | 0.983 | D | 0.435 | neutral | None | None | None | None | N |
| S/Y | 0.1665 | likely_benign | 0.1376 | benign | -0.597 | Destabilizing | 0.921 | D | 0.394 | 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.