Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8011 | 24256;24257;24258 | chr2:178719359;178719358;178719357 | chr2:179584086;179584085;179584084 |
| N2AB | 7694 | 23305;23306;23307 | chr2:178719359;178719358;178719357 | chr2:179584086;179584085;179584084 |
| N2A | 6767 | 20524;20525;20526 | chr2:178719359;178719358;178719357 | chr2:179584086;179584085;179584084 |
| 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/L | rs771628562  |
0.124 | 0.014 | N | 0.436 | 0.345 | 0.510113526977 | gnomAD-4.0.0 | 1.59125E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85837E-06 | 0 | 0 |
| S/P | rs774921957 |
-0.096 | 0.97 | N | 0.475 | 0.392 | 0.426787303895 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.95E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs774921957 |
-0.096 | 0.97 | N | 0.475 | 0.392 | 0.426787303895 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs774921957 |
-0.096 | 0.97 | N | 0.475 | 0.392 | 0.426787303895 | gnomAD-4.0.0 | 6.8168E-06 | None | None | None | None | I | None | 1.33515E-05 | 0 | None | 1.68919E-04 | 0 | None | 0 | 1.64528E-04 | 2.54291E-06 | 0 | 1.60102E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2341 | likely_benign | 0.2996 | benign | -0.107 | Destabilizing | 0.489 | N | 0.428 | neutral | N | 0.509950611 | None | None | I |
| S/C | 0.4332 | ambiguous | 0.5585 | ambiguous | -0.394 | Destabilizing | 0.998 | D | 0.513 | neutral | None | None | None | None | I |
| S/D | 0.8737 | likely_pathogenic | 0.8895 | pathogenic | 0.017 | Stabilizing | 0.86 | D | 0.432 | neutral | None | None | None | None | I |
| S/E | 0.9409 | likely_pathogenic | 0.9516 | pathogenic | -0.082 | Destabilizing | 0.86 | D | 0.438 | neutral | None | None | None | None | I |
| S/F | 0.7105 | likely_pathogenic | 0.7931 | pathogenic | -0.818 | Destabilizing | 0.956 | D | 0.623 | neutral | None | None | None | None | I |
| S/G | 0.3007 | likely_benign | 0.3637 | ambiguous | -0.171 | Destabilizing | 0.86 | D | 0.43 | neutral | None | None | None | None | I |
| S/H | 0.8575 | likely_pathogenic | 0.8864 | pathogenic | -0.49 | Destabilizing | 0.998 | D | 0.497 | neutral | None | None | None | None | I |
| S/I | 0.7435 | likely_pathogenic | 0.8146 | pathogenic | -0.073 | Destabilizing | 0.915 | D | 0.567 | neutral | None | None | None | None | I |
| S/K | 0.9857 | likely_pathogenic | 0.9892 | pathogenic | -0.41 | Destabilizing | 0.86 | D | 0.437 | neutral | None | None | None | None | I |
| S/L | 0.4283 | ambiguous | 0.5019 | ambiguous | -0.073 | Destabilizing | 0.014 | N | 0.436 | neutral | N | 0.492151244 | None | None | I |
| S/M | 0.6433 | likely_pathogenic | 0.6976 | pathogenic | -0.153 | Destabilizing | 0.956 | D | 0.482 | neutral | None | None | None | None | I |
| S/N | 0.5805 | likely_pathogenic | 0.6568 | pathogenic | -0.173 | Destabilizing | 0.86 | D | 0.459 | neutral | None | None | None | None | I |
| S/P | 0.881 | likely_pathogenic | 0.9165 | pathogenic | -0.059 | Destabilizing | 0.97 | D | 0.475 | neutral | N | 0.515788908 | None | None | I |
| S/Q | 0.9318 | likely_pathogenic | 0.9456 | pathogenic | -0.38 | Destabilizing | 0.978 | D | 0.425 | neutral | None | None | None | None | I |
| S/R | 0.9716 | likely_pathogenic | 0.9784 | pathogenic | -0.153 | Destabilizing | 0.978 | D | 0.473 | neutral | None | None | None | None | I |
| S/T | 0.2272 | likely_benign | 0.2563 | benign | -0.254 | Destabilizing | 0.058 | N | 0.282 | neutral | N | 0.49873354 | None | None | I |
| S/V | 0.6987 | likely_pathogenic | 0.7745 | pathogenic | -0.059 | Destabilizing | 0.754 | D | 0.579 | neutral | None | None | None | None | I |
| S/W | 0.8093 | likely_pathogenic | 0.865 | pathogenic | -0.92 | Destabilizing | 0.998 | D | 0.707 | prob.neutral | None | None | None | None | I |
| S/Y | 0.6625 | likely_pathogenic | 0.7413 | pathogenic | -0.59 | Destabilizing | 0.978 | D | 0.629 | neutral | None | None | None | None | I |
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.