Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2775 | 8548;8549;8550 | chr2:178770469;178770468;178770467 | chr2:179635196;179635195;179635194 |
| N2AB | 2775 | 8548;8549;8550 | chr2:178770469;178770468;178770467 | chr2:179635196;179635195;179635194 |
| N2A | 2775 | 8548;8549;8550 | chr2:178770469;178770468;178770467 | chr2:179635196;179635195;179635194 |
| N2B | 2729 | 8410;8411;8412 | chr2:178770469;178770468;178770467 | chr2:179635196;179635195;179635194 |
| Novex-1 | 2729 | 8410;8411;8412 | chr2:178770469;178770468;178770467 | chr2:179635196;179635195;179635194 |
| Novex-2 | 2729 | 8410;8411;8412 | chr2:178770469;178770468;178770467 | chr2:179635196;179635195;179635194 |
| Novex-3 | 2775 | 8548;8549;8550 | chr2:178770469;178770468;178770467 | chr2:179635196;179635195;179635194 |
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/C | None | None | 1.0 | D | 0.74 | 0.555 | 0.700396112747 | gnomAD-4.0.0 | 1.59053E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85646E-06 | 0 | 0 |
| S/F | rs1422746407  |
-1.033 | 0.999 | D | 0.771 | 0.576 | 0.837991807345 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| S/F | rs1422746407 |
-1.033 | 0.999 | D | 0.771 | 0.576 | 0.837991807345 | gnomAD-4.0.0 | 1.59053E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85646E-06 | 0 | 0 |
| S/P | rs755629576 |
-0.68 | 0.999 | D | 0.751 | 0.602 | 0.513226221338 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | I | None | 1.23031E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs755629576 |
-0.68 | 0.999 | D | 0.751 | 0.602 | 0.513226221338 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.66E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs755629576 |
-0.68 | 0.999 | D | 0.751 | 0.602 | 0.513226221338 | gnomAD-4.0.0 | 2.63061E-05 | None | None | None | None | I | None | 9.66464E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0959 | likely_benign | 0.0986 | benign | -0.489 | Destabilizing | 0.973 | D | 0.637 | neutral | N | 0.5090233 | None | None | I |
| S/C | 0.2146 | likely_benign | 0.2338 | benign | -0.37 | Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.553797386 | None | None | I |
| S/D | 0.8033 | likely_pathogenic | 0.8422 | pathogenic | 0.243 | Stabilizing | 0.996 | D | 0.705 | prob.neutral | None | None | None | None | I |
| S/E | 0.9245 | likely_pathogenic | 0.9322 | pathogenic | 0.195 | Stabilizing | 0.996 | D | 0.7 | prob.neutral | None | None | None | None | I |
| S/F | 0.707 | likely_pathogenic | 0.7684 | pathogenic | -0.933 | Destabilizing | 0.999 | D | 0.771 | deleterious | D | 0.619357687 | None | None | I |
| S/G | 0.1178 | likely_benign | 0.1404 | benign | -0.658 | Destabilizing | 0.996 | D | 0.667 | neutral | None | None | None | None | I |
| S/H | 0.8508 | likely_pathogenic | 0.8697 | pathogenic | -1.028 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| S/I | 0.7325 | likely_pathogenic | 0.7786 | pathogenic | -0.165 | Destabilizing | 0.998 | D | 0.755 | deleterious | None | None | None | None | I |
| S/K | 0.9828 | likely_pathogenic | 0.9851 | pathogenic | -0.497 | Destabilizing | 0.996 | D | 0.705 | prob.neutral | None | None | None | None | I |
| S/L | 0.3461 | ambiguous | 0.4196 | ambiguous | -0.165 | Destabilizing | 0.992 | D | 0.74 | deleterious | None | None | None | None | I |
| S/M | 0.4577 | ambiguous | 0.5151 | ambiguous | -0.127 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| S/N | 0.3793 | ambiguous | 0.4431 | ambiguous | -0.335 | Destabilizing | 0.996 | D | 0.697 | prob.neutral | None | None | None | None | I |
| S/P | 0.9868 | likely_pathogenic | 0.9923 | pathogenic | -0.242 | Destabilizing | 0.999 | D | 0.751 | deleterious | D | 0.618320192 | None | None | I |
| S/Q | 0.9099 | likely_pathogenic | 0.9137 | pathogenic | -0.47 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| S/R | 0.9674 | likely_pathogenic | 0.9711 | pathogenic | -0.326 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | I |
| S/T | 0.1939 | likely_benign | 0.2005 | benign | -0.395 | Destabilizing | 0.543 | D | 0.505 | neutral | D | 0.576956738 | None | None | I |
| S/V | 0.6211 | likely_pathogenic | 0.6579 | pathogenic | -0.242 | Destabilizing | 0.998 | D | 0.741 | deleterious | None | None | None | None | I |
| S/W | 0.8818 | likely_pathogenic | 0.9125 | pathogenic | -0.965 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| S/Y | 0.6475 | likely_pathogenic | 0.7339 | pathogenic | -0.673 | Destabilizing | 0.999 | D | 0.77 | deleterious | D | 0.619357687 | 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.