Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32526 | 97801;97802;97803 | chr2:178541501;178541500;178541499 | chr2:179406228;179406227;179406226 |
| N2AB | 30885 | 92878;92879;92880 | chr2:178541501;178541500;178541499 | chr2:179406228;179406227;179406226 |
| N2A | 29958 | 90097;90098;90099 | chr2:178541501;178541500;178541499 | chr2:179406228;179406227;179406226 |
| N2B | 23461 | 70606;70607;70608 | chr2:178541501;178541500;178541499 | chr2:179406228;179406227;179406226 |
| Novex-1 | 23586 | 70981;70982;70983 | chr2:178541501;178541500;178541499 | chr2:179406228;179406227;179406226 |
| Novex-2 | 23653 | 71182;71183;71184 | chr2:178541501;178541500;178541499 | chr2:179406228;179406227;179406226 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs142907833  |
-0.43 | 0.979 | N | 0.467 | 0.373 | 0.218112801441 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/E | rs142907833 |
-0.43 | 0.979 | N | 0.467 | 0.373 | 0.218112801441 | 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 |
| D/E | rs142907833 |
-0.43 | 0.979 | N | 0.467 | 0.373 | 0.218112801441 | gnomAD-4.0.0 | 2.66554E-05 | None | None | None | None | I | None | 0 | 1.66789E-05 | None | 0 | 0 | None | 0 | 0 | 3.5607E-05 | 0 | 0 |
| D/V | None | None | 0.999 | N | 0.753 | 0.571 | 0.694889576946 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4541 | ambiguous | 0.529 | ambiguous | -0.276 | Destabilizing | 0.989 | D | 0.644 | neutral | N | 0.489437041 | None | None | I |
| D/C | 0.8081 | likely_pathogenic | 0.8606 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| D/E | 0.5308 | ambiguous | 0.6004 | pathogenic | -0.424 | Destabilizing | 0.979 | D | 0.467 | neutral | N | 0.488423083 | None | None | I |
| D/F | 0.8686 | likely_pathogenic | 0.9064 | pathogenic | -0.565 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/G | 0.4108 | ambiguous | 0.4873 | ambiguous | -0.467 | Destabilizing | 0.978 | D | 0.566 | neutral | N | 0.505605966 | None | None | I |
| D/H | 0.5752 | likely_pathogenic | 0.6656 | pathogenic | -0.762 | Destabilizing | 0.997 | D | 0.707 | prob.neutral | N | 0.499085053 | None | None | I |
| D/I | 0.7179 | likely_pathogenic | 0.7846 | pathogenic | 0.175 | Stabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | I |
| D/K | 0.7616 | likely_pathogenic | 0.84 | pathogenic | 0.33 | Stabilizing | 0.983 | D | 0.617 | neutral | None | None | None | None | I |
| D/L | 0.7474 | likely_pathogenic | 0.8093 | pathogenic | 0.175 | Stabilizing | 0.998 | D | 0.741 | deleterious | None | None | None | None | I |
| D/M | 0.8586 | likely_pathogenic | 0.8884 | pathogenic | 0.567 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| D/N | 0.1147 | likely_benign | 0.1233 | benign | 0.141 | Stabilizing | 0.198 | N | 0.186 | neutral | N | 0.49179642 | None | None | I |
| D/P | 0.8872 | likely_pathogenic | 0.911 | pathogenic | 0.047 | Stabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/Q | 0.7392 | likely_pathogenic | 0.8112 | pathogenic | 0.15 | Stabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | I |
| D/R | 0.7662 | likely_pathogenic | 0.8346 | pathogenic | 0.228 | Stabilizing | 0.998 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/S | 0.209 | likely_benign | 0.2328 | benign | 0.04 | Stabilizing | 0.983 | D | 0.579 | neutral | None | None | None | None | I |
| D/T | 0.3321 | likely_benign | 0.3655 | ambiguous | 0.187 | Stabilizing | 0.983 | D | 0.614 | neutral | None | None | None | None | I |
| D/V | 0.5642 | likely_pathogenic | 0.6461 | pathogenic | 0.047 | Stabilizing | 0.999 | D | 0.753 | deleterious | N | 0.496932232 | None | None | I |
| D/W | 0.9666 | likely_pathogenic | 0.9785 | pathogenic | -0.546 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/Y | 0.5049 | ambiguous | 0.5993 | pathogenic | -0.355 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | N | 0.511201827 | 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.