Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23844 | 71755;71756;71757 | chr2:178574602;178574601;178574600 | chr2:179439329;179439328;179439327 |
| N2AB | 22203 | 66832;66833;66834 | chr2:178574602;178574601;178574600 | chr2:179439329;179439328;179439327 |
| N2A | 21276 | 64051;64052;64053 | chr2:178574602;178574601;178574600 | chr2:179439329;179439328;179439327 |
| N2B | 14779 | 44560;44561;44562 | chr2:178574602;178574601;178574600 | chr2:179439329;179439328;179439327 |
| Novex-1 | 14904 | 44935;44936;44937 | chr2:178574602;178574601;178574600 | chr2:179439329;179439328;179439327 |
| Novex-2 | 14971 | 45136;45137;45138 | chr2:178574602;178574601;178574600 | chr2:179439329;179439328;179439327 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | None | None | 0.801 | N | 0.691 | 0.278 | 0.398872588132 | gnomAD-4.0.0 | 1.59218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85987E-06 | 0 | 0 |
| T/P | rs753837961  |
-0.67 | 0.966 | N | 0.717 | 0.417 | 0.464442853059 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/P | rs753837961 |
-0.67 | 0.966 | N | 0.717 | 0.417 | 0.464442853059 | gnomAD-4.0.0 | 3.18452E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86722E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1073 | likely_benign | 0.0994 | benign | -1.14 | Destabilizing | 0.454 | N | 0.546 | neutral | N | 0.478258546 | None | None | N |
| T/C | 0.3948 | ambiguous | 0.3533 | ambiguous | -0.984 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/D | 0.5145 | ambiguous | 0.5035 | ambiguous | -0.945 | Destabilizing | 0.949 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/E | 0.3541 | ambiguous | 0.3498 | ambiguous | -0.846 | Destabilizing | 0.842 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/F | 0.2351 | likely_benign | 0.2261 | benign | -0.992 | Destabilizing | 0.949 | D | 0.725 | prob.delet. | None | None | None | None | N |
| T/G | 0.3613 | ambiguous | 0.3374 | benign | -1.472 | Destabilizing | 0.728 | D | 0.672 | neutral | None | None | None | None | N |
| T/H | 0.3071 | likely_benign | 0.2947 | benign | -1.639 | Destabilizing | 0.998 | D | 0.732 | prob.delet. | None | None | None | None | N |
| T/I | 0.1285 | likely_benign | 0.1157 | benign | -0.31 | Destabilizing | 0.669 | D | 0.629 | neutral | N | 0.471599502 | None | None | N |
| T/K | 0.3341 | likely_benign | 0.3185 | benign | -0.758 | Destabilizing | 0.801 | D | 0.691 | prob.neutral | N | 0.476372442 | None | None | N |
| T/L | 0.0903 | likely_benign | 0.0868 | benign | -0.31 | Destabilizing | 0.525 | D | 0.605 | neutral | None | None | None | None | N |
| T/M | 0.0798 | likely_benign | 0.0756 | benign | -0.204 | Destabilizing | 0.525 | D | 0.529 | neutral | None | None | None | None | N |
| T/N | 0.1529 | likely_benign | 0.1456 | benign | -1.06 | Destabilizing | 0.949 | D | 0.649 | neutral | None | None | None | None | N |
| T/P | 0.7843 | likely_pathogenic | 0.6837 | pathogenic | -0.555 | Destabilizing | 0.966 | D | 0.717 | prob.delet. | N | 0.516886593 | None | None | N |
| T/Q | 0.2595 | likely_benign | 0.2579 | benign | -1.104 | Destabilizing | 0.974 | D | 0.735 | prob.delet. | None | None | None | None | N |
| T/R | 0.2833 | likely_benign | 0.2571 | benign | -0.683 | Destabilizing | 0.934 | D | 0.735 | prob.delet. | N | 0.482195339 | None | None | N |
| T/S | 0.1375 | likely_benign | 0.1349 | benign | -1.35 | Destabilizing | 0.051 | N | 0.434 | neutral | N | 0.509438031 | None | None | N |
| T/V | 0.1058 | likely_benign | 0.0992 | benign | -0.555 | Destabilizing | 0.016 | N | 0.228 | neutral | None | None | None | None | N |
| T/W | 0.6138 | likely_pathogenic | 0.5738 | pathogenic | -0.955 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | N |
| T/Y | 0.2783 | likely_benign | 0.2635 | benign | -0.666 | Destabilizing | 0.991 | D | 0.735 | 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.