Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24249 | 72970;72971;72972 | chr2:178573387;178573386;178573385 | chr2:179438114;179438113;179438112 |
| N2AB | 22608 | 68047;68048;68049 | chr2:178573387;178573386;178573385 | chr2:179438114;179438113;179438112 |
| N2A | 21681 | 65266;65267;65268 | chr2:178573387;178573386;178573385 | chr2:179438114;179438113;179438112 |
| N2B | 15184 | 45775;45776;45777 | chr2:178573387;178573386;178573385 | chr2:179438114;179438113;179438112 |
| Novex-1 | 15309 | 46150;46151;46152 | chr2:178573387;178573386;178573385 | chr2:179438114;179438113;179438112 |
| Novex-2 | 15376 | 46351;46352;46353 | chr2:178573387;178573386;178573385 | chr2:179438114;179438113;179438112 |
| 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/H | None | None | 1.0 | N | 0.743 | 0.394 | 0.366277470483 | gnomAD-4.0.0 | 2.91475E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.74023E-06 | 0 | 0 |
| D/V | rs760835469  |
0.404 | 1.0 | D | 0.739 | 0.535 | 0.62298222662 | gnomAD-2.1.1 | 5.56E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.15E-05 | 0 |
| D/V | rs760835469 |
0.404 | 1.0 | D | 0.739 | 0.535 | 0.62298222662 | gnomAD-4.0.0 | 1.85489E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.41787E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6311 | likely_pathogenic | 0.5867 | pathogenic | -0.19 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | N | 0.505566286 | None | None | I |
| D/C | 0.9145 | likely_pathogenic | 0.9158 | pathogenic | 0.252 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| D/E | 0.705 | likely_pathogenic | 0.7104 | pathogenic | -0.614 | Destabilizing | 0.992 | D | 0.452 | neutral | N | 0.506856506 | None | None | I |
| D/F | 0.9538 | likely_pathogenic | 0.938 | pathogenic | -0.527 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/G | 0.6247 | likely_pathogenic | 0.554 | ambiguous | -0.425 | Destabilizing | 0.992 | D | 0.653 | neutral | D | 0.526343567 | None | None | I |
| D/H | 0.7721 | likely_pathogenic | 0.7585 | pathogenic | -0.86 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.508466348 | None | None | I |
| D/I | 0.8812 | likely_pathogenic | 0.8608 | pathogenic | 0.382 | Stabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| D/K | 0.8971 | likely_pathogenic | 0.8746 | pathogenic | 0.238 | Stabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | I |
| D/L | 0.8716 | likely_pathogenic | 0.8489 | pathogenic | 0.382 | Stabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | I |
| D/M | 0.9439 | likely_pathogenic | 0.9332 | pathogenic | 0.829 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/N | 0.1141 | likely_benign | 0.1209 | benign | -0.02 | Destabilizing | 0.79 | D | 0.265 | neutral | N | 0.503917568 | None | None | I |
| D/P | 0.9293 | likely_pathogenic | 0.9165 | pathogenic | 0.215 | Stabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| D/Q | 0.8781 | likely_pathogenic | 0.8586 | pathogenic | 0.026 | Stabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | I |
| D/R | 0.9004 | likely_pathogenic | 0.8745 | pathogenic | 0.093 | Stabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | I |
| D/S | 0.2628 | likely_benign | 0.2381 | benign | -0.138 | Destabilizing | 0.994 | D | 0.643 | neutral | None | None | None | None | I |
| D/T | 0.4839 | ambiguous | 0.4257 | ambiguous | 0.051 | Stabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/V | 0.7547 | likely_pathogenic | 0.7133 | pathogenic | 0.215 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.52507612 | None | None | I |
| D/W | 0.9916 | likely_pathogenic | 0.9893 | pathogenic | -0.557 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/Y | 0.7548 | likely_pathogenic | 0.6908 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | D | 0.552841613 | 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.