Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1538 | 4837;4838;4839 | chr2:178777453;178777452;178777451 | chr2:179642180;179642179;179642178 |
| N2AB | 1538 | 4837;4838;4839 | chr2:178777453;178777452;178777451 | chr2:179642180;179642179;179642178 |
| N2A | 1538 | 4837;4838;4839 | chr2:178777453;178777452;178777451 | chr2:179642180;179642179;179642178 |
| N2B | 1492 | 4699;4700;4701 | chr2:178777453;178777452;178777451 | chr2:179642180;179642179;179642178 |
| Novex-1 | 1492 | 4699;4700;4701 | chr2:178777453;178777452;178777451 | chr2:179642180;179642179;179642178 |
| Novex-2 | 1492 | 4699;4700;4701 | chr2:178777453;178777452;178777451 | chr2:179642180;179642179;179642178 |
| Novex-3 | 1538 | 4837;4838;4839 | chr2:178777453;178777452;178777451 | chr2:179642180;179642179;179642178 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs766463184  |
-0.551 | 0.117 | N | 0.528 | 0.231 | 0.533325340949 | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | I | None | 0 | 1.15935E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs766463184 |
-0.551 | 0.117 | N | 0.528 | 0.231 | 0.533325340949 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs766463184 |
-0.551 | 0.117 | N | 0.528 | 0.231 | 0.533325340949 | gnomAD-4.0.0 | 7.68586E-06 | None | None | None | None | I | None | 0 | 1.01726E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/I | rs753961168 |
None | 0.484 | N | 0.535 | 0.191 | 0.520110530135 | gnomAD-4.0.0 | 2.05264E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79876E-06 | 1.15945E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3574 | ambiguous | 0.4071 | ambiguous | -0.299 | Destabilizing | 0.035 | N | 0.47 | neutral | None | None | None | None | I |
| R/C | 0.2566 | likely_benign | 0.2792 | benign | -0.473 | Destabilizing | 0.935 | D | 0.521 | neutral | None | None | None | None | I |
| R/D | 0.7383 | likely_pathogenic | 0.791 | pathogenic | -0.088 | Destabilizing | 0.149 | N | 0.55 | neutral | None | None | None | None | I |
| R/E | 0.3125 | likely_benign | 0.3513 | ambiguous | -0.019 | Destabilizing | 0.035 | N | 0.368 | neutral | None | None | None | None | I |
| R/F | 0.5978 | likely_pathogenic | 0.6449 | pathogenic | -0.484 | Destabilizing | 0.791 | D | 0.523 | neutral | None | None | None | None | I |
| R/G | 0.3166 | likely_benign | 0.3671 | ambiguous | -0.504 | Destabilizing | 0.117 | N | 0.528 | neutral | N | 0.505334028 | None | None | I |
| R/H | 0.1355 | likely_benign | 0.1427 | benign | -0.85 | Destabilizing | 0.555 | D | 0.436 | neutral | None | None | None | None | I |
| R/I | 0.2518 | likely_benign | 0.2738 | benign | 0.212 | Stabilizing | 0.484 | N | 0.535 | neutral | N | 0.501885811 | None | None | I |
| R/K | 0.0597 | likely_benign | 0.0609 | benign | -0.377 | Destabilizing | None | N | 0.201 | neutral | N | 0.40776645 | None | None | I |
| R/L | 0.2562 | likely_benign | 0.2803 | benign | 0.212 | Stabilizing | 0.149 | N | 0.528 | neutral | None | None | None | None | I |
| R/M | 0.2229 | likely_benign | 0.2463 | benign | -0.152 | Destabilizing | 0.791 | D | 0.502 | neutral | None | None | None | None | I |
| R/N | 0.4934 | ambiguous | 0.5522 | ambiguous | -0.103 | Destabilizing | 0.149 | N | 0.375 | neutral | None | None | None | None | I |
| R/P | 0.8908 | likely_pathogenic | 0.912 | pathogenic | 0.062 | Stabilizing | 0.262 | N | 0.523 | neutral | None | None | None | None | I |
| R/Q | 0.0963 | likely_benign | 0.1008 | benign | -0.247 | Destabilizing | 0.081 | N | 0.391 | neutral | None | None | None | None | I |
| R/S | 0.3904 | ambiguous | 0.4427 | ambiguous | -0.594 | Destabilizing | 0.027 | N | 0.471 | neutral | N | 0.45693618 | None | None | I |
| R/T | 0.1881 | likely_benign | 0.2101 | benign | -0.384 | Destabilizing | 0.117 | N | 0.482 | neutral | N | 0.479961199 | None | None | I |
| R/V | 0.3206 | likely_benign | 0.3489 | ambiguous | 0.062 | Stabilizing | 0.149 | N | 0.571 | neutral | None | None | None | None | I |
| R/W | 0.2782 | likely_benign | 0.3028 | benign | -0.431 | Destabilizing | 0.935 | D | 0.528 | neutral | None | None | None | None | I |
| R/Y | 0.469 | ambiguous | 0.5151 | ambiguous | -0.053 | Destabilizing | 0.555 | D | 0.534 | 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.