Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18182 | 54769;54770;54771 | chr2:178604143;178604142;178604141 | chr2:179468870;179468869;179468868 |
| N2AB | 16541 | 49846;49847;49848 | chr2:178604143;178604142;178604141 | chr2:179468870;179468869;179468868 |
| N2A | 15614 | 47065;47066;47067 | chr2:178604143;178604142;178604141 | chr2:179468870;179468869;179468868 |
| N2B | 9117 | 27574;27575;27576 | chr2:178604143;178604142;178604141 | chr2:179468870;179468869;179468868 |
| Novex-1 | 9242 | 27949;27950;27951 | chr2:178604143;178604142;178604141 | chr2:179468870;179468869;179468868 |
| Novex-2 | 9309 | 28150;28151;28152 | chr2:178604143;178604142;178604141 | chr2:179468870;179468869;179468868 |
| 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/L | rs1470054004  |
None | 0.997 | D | 0.675 | 0.472 | 0.737862570375 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/L | rs1470054004 |
None | 0.997 | D | 0.675 | 0.472 | 0.737862570375 | gnomAD-4.0.0 | 2.56678E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39737E-06 | 1.34271E-05 | 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 | 0.1271 | likely_benign | 0.1133 | benign | -0.414 | Destabilizing | 0.973 | D | 0.495 | neutral | N | 0.515678931 | None | None | N |
| S/C | 0.1294 | likely_benign | 0.1311 | benign | -0.617 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| S/D | 0.6839 | likely_pathogenic | 0.6483 | pathogenic | -1.531 | Destabilizing | 0.992 | D | 0.544 | neutral | None | None | None | None | N |
| S/E | 0.6866 | likely_pathogenic | 0.666 | pathogenic | -1.511 | Destabilizing | 0.983 | D | 0.533 | neutral | None | None | None | None | N |
| S/F | 0.2807 | likely_benign | 0.2239 | benign | -0.787 | Destabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| S/G | 0.1599 | likely_benign | 0.1252 | benign | -0.651 | Destabilizing | 0.992 | D | 0.509 | neutral | None | None | None | None | N |
| S/H | 0.4382 | ambiguous | 0.3964 | ambiguous | -1.301 | Destabilizing | 0.296 | N | 0.381 | neutral | None | None | None | None | N |
| S/I | 0.3942 | ambiguous | 0.3744 | ambiguous | 0.106 | Stabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/K | 0.8737 | likely_pathogenic | 0.8714 | pathogenic | -0.724 | Destabilizing | 0.983 | D | 0.551 | neutral | None | None | None | None | N |
| S/L | 0.2144 | likely_benign | 0.1794 | benign | 0.106 | Stabilizing | 0.997 | D | 0.675 | prob.neutral | D | 0.526301704 | None | None | N |
| S/M | 0.2824 | likely_benign | 0.2529 | benign | 0.432 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/N | 0.2095 | likely_benign | 0.2137 | benign | -1.027 | Destabilizing | 0.983 | D | 0.538 | neutral | None | None | None | None | N |
| S/P | 0.9723 | likely_pathogenic | 0.9599 | pathogenic | -0.034 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.508197449 | None | None | N |
| S/Q | 0.5876 | likely_pathogenic | 0.5738 | pathogenic | -1.232 | Destabilizing | 0.998 | D | 0.607 | neutral | None | None | None | None | N |
| S/R | 0.8233 | likely_pathogenic | 0.8067 | pathogenic | -0.598 | Destabilizing | 0.995 | D | 0.685 | prob.neutral | None | None | None | None | N |
| S/T | 0.1299 | likely_benign | 0.1265 | benign | -0.789 | Destabilizing | 0.989 | D | 0.517 | neutral | N | 0.478928697 | None | None | N |
| S/V | 0.346 | ambiguous | 0.3304 | benign | -0.034 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| S/W | 0.5423 | ambiguous | 0.4565 | ambiguous | -0.926 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| S/Y | 0.2672 | likely_benign | 0.2328 | benign | -0.54 | Destabilizing | 0.995 | D | 0.71 | prob.delet. | 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.