Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17758 | 53497;53498;53499 | chr2:178607416;178607415;178607414 | chr2:179472143;179472142;179472141 |
| N2AB | 16117 | 48574;48575;48576 | chr2:178607416;178607415;178607414 | chr2:179472143;179472142;179472141 |
| N2A | 15190 | 45793;45794;45795 | chr2:178607416;178607415;178607414 | chr2:179472143;179472142;179472141 |
| N2B | 8693 | 26302;26303;26304 | chr2:178607416;178607415;178607414 | chr2:179472143;179472142;179472141 |
| Novex-1 | 8818 | 26677;26678;26679 | chr2:178607416;178607415;178607414 | chr2:179472143;179472142;179472141 |
| Novex-2 | 8885 | 26878;26879;26880 | chr2:178607416;178607415;178607414 | chr2:179472143;179472142;179472141 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/M | None | None | 1.0 | N | 0.709 | 0.416 | 0.6236463853 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| R/S | rs755982578  |
-0.439 | 0.978 | N | 0.659 | 0.376 | 0.403609169532 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 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 | 0.6473 | likely_pathogenic | 0.5575 | ambiguous | -0.329 | Destabilizing | 0.992 | D | 0.649 | neutral | None | None | None | None | I |
| R/C | 0.379 | ambiguous | 0.3182 | benign | -0.216 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| R/D | 0.839 | likely_pathogenic | 0.788 | pathogenic | 0.061 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| R/E | 0.6302 | likely_pathogenic | 0.5706 | pathogenic | 0.163 | Stabilizing | 0.996 | D | 0.638 | neutral | None | None | None | None | I |
| R/F | 0.7111 | likely_pathogenic | 0.6452 | pathogenic | -0.282 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| R/G | 0.6047 | likely_pathogenic | 0.4934 | ambiguous | -0.611 | Destabilizing | 0.994 | D | 0.657 | neutral | N | 0.495834547 | None | None | I |
| R/H | 0.197 | likely_benign | 0.1653 | benign | -1.086 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| R/I | 0.3978 | ambiguous | 0.3487 | ambiguous | 0.408 | Stabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/K | 0.1747 | likely_benign | 0.1542 | benign | -0.322 | Destabilizing | 0.987 | D | 0.533 | neutral | N | 0.441128031 | None | None | I |
| R/L | 0.4164 | ambiguous | 0.3498 | ambiguous | 0.408 | Stabilizing | 0.992 | D | 0.656 | neutral | None | None | None | None | I |
| R/M | 0.4432 | ambiguous | 0.3842 | ambiguous | 0.043 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.485238711 | None | None | I |
| R/N | 0.7608 | likely_pathogenic | 0.6998 | pathogenic | 0.18 | Stabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| R/P | 0.8546 | likely_pathogenic | 0.7313 | pathogenic | 0.184 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/Q | 0.2118 | likely_benign | 0.181 | benign | 0.024 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/S | 0.7382 | likely_pathogenic | 0.6428 | pathogenic | -0.409 | Destabilizing | 0.978 | D | 0.659 | neutral | N | 0.468986636 | None | None | I |
| R/T | 0.4393 | ambiguous | 0.3565 | ambiguous | -0.139 | Destabilizing | 0.543 | D | 0.445 | neutral | N | 0.440954673 | None | None | I |
| R/V | 0.4818 | ambiguous | 0.4154 | ambiguous | 0.184 | Stabilizing | 0.998 | D | 0.662 | neutral | None | None | None | None | I |
| R/W | 0.3067 | likely_benign | 0.249 | benign | -0.093 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.496848506 | None | None | I |
| R/Y | 0.602 | likely_pathogenic | 0.5294 | ambiguous | 0.247 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | 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.