Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34393 | 103402;103403;103404 | chr2:178533438;178533437;178533436 | chr2:179398165;179398164;179398163 |
| N2AB | 32752 | 98479;98480;98481 | chr2:178533438;178533437;178533436 | chr2:179398165;179398164;179398163 |
| N2A | 31825 | 95698;95699;95700 | chr2:178533438;178533437;178533436 | chr2:179398165;179398164;179398163 |
| N2B | 25328 | 76207;76208;76209 | chr2:178533438;178533437;178533436 | chr2:179398165;179398164;179398163 |
| Novex-1 | 25453 | 76582;76583;76584 | chr2:178533438;178533437;178533436 | chr2:179398165;179398164;179398163 |
| Novex-2 | 25520 | 76783;76784;76785 | chr2:178533438;178533437;178533436 | chr2:179398165;179398164;179398163 |
| 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/I | rs372299779  |
0.069 | 0.988 | N | 0.521 | 0.37 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/I | rs372299779 |
0.069 | 0.988 | N | 0.521 | 0.37 | None | gnomAD-4.0.0 | 5.4735E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.1954E-06 | 0 | 0 |
| T/P | rs947426325 |
-0.226 | 0.988 | N | 0.513 | 0.507 | 0.452450644169 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/P | rs947426325 |
-0.226 | 0.988 | N | 0.513 | 0.507 | 0.452450644169 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| T/P | rs947426325 |
-0.226 | 0.988 | N | 0.513 | 0.507 | 0.452450644169 | gnomAD-4.0.0 | 1.05346E-05 | None | None | None | None | I | None | 0 | 3.33367E-05 | None | 0 | 0 | None | 0 | 0 | 1.18661E-05 | 0 | 1.60097E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1009 | likely_benign | 0.0855 | benign | -0.567 | Destabilizing | 0.704 | D | 0.373 | neutral | N | 0.51172148 | None | None | I |
| T/C | 0.547 | ambiguous | 0.5093 | ambiguous | -0.281 | Destabilizing | 0.999 | D | 0.54 | neutral | None | None | None | None | I |
| T/D | 0.4377 | ambiguous | 0.3598 | ambiguous | 0.02 | Stabilizing | 0.884 | D | 0.419 | neutral | None | None | None | None | I |
| T/E | 0.2906 | likely_benign | 0.2462 | benign | -0.023 | Destabilizing | 0.17 | N | 0.291 | neutral | None | None | None | None | I |
| T/F | 0.3234 | likely_benign | 0.2622 | benign | -0.832 | Destabilizing | 0.997 | D | 0.639 | neutral | None | None | None | None | I |
| T/G | 0.4017 | ambiguous | 0.3451 | ambiguous | -0.768 | Destabilizing | 0.939 | D | 0.475 | neutral | None | None | None | None | I |
| T/H | 0.2742 | likely_benign | 0.2307 | benign | -1.078 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | I |
| T/I | 0.1564 | likely_benign | 0.1274 | benign | -0.14 | Destabilizing | 0.988 | D | 0.521 | neutral | N | 0.484758185 | None | None | I |
| T/K | 0.2157 | likely_benign | 0.188 | benign | -0.594 | Destabilizing | 0.92 | D | 0.439 | neutral | N | 0.48976734 | None | None | I |
| T/L | 0.1256 | likely_benign | 0.103 | benign | -0.14 | Destabilizing | 0.969 | D | 0.435 | neutral | None | None | None | None | I |
| T/M | 0.1155 | likely_benign | 0.0976 | benign | 0.095 | Stabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | I |
| T/N | 0.1506 | likely_benign | 0.1295 | benign | -0.379 | Destabilizing | 0.939 | D | 0.376 | neutral | None | None | None | None | I |
| T/P | 0.6221 | likely_pathogenic | 0.5156 | ambiguous | -0.251 | Destabilizing | 0.988 | D | 0.513 | neutral | N | 0.514890308 | None | None | I |
| T/Q | 0.2125 | likely_benign | 0.1873 | benign | -0.572 | Destabilizing | 0.982 | D | 0.509 | neutral | None | None | None | None | I |
| T/R | 0.2048 | likely_benign | 0.1769 | benign | -0.336 | Destabilizing | 0.976 | D | 0.513 | neutral | N | 0.48828726 | None | None | I |
| T/S | 0.1174 | likely_benign | 0.1038 | benign | -0.615 | Destabilizing | 0.159 | N | 0.161 | neutral | N | 0.467005123 | None | None | I |
| T/V | 0.1243 | likely_benign | 0.1024 | benign | -0.251 | Destabilizing | 0.969 | D | 0.343 | neutral | None | None | None | None | I |
| T/W | 0.8023 | likely_pathogenic | 0.7537 | pathogenic | -0.807 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | I |
| T/Y | 0.4108 | ambiguous | 0.3451 | ambiguous | -0.562 | Destabilizing | 0.997 | D | 0.639 | 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.