Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14334 | 43225;43226;43227 | chr2:178633273;178633272;178633271 | chr2:179498000;179497999;179497998 |
| N2AB | 12693 | 38302;38303;38304 | chr2:178633273;178633272;178633271 | chr2:179498000;179497999;179497998 |
| N2A | 11766 | 35521;35522;35523 | chr2:178633273;178633272;178633271 | chr2:179498000;179497999;179497998 |
| N2B | 5269 | 16030;16031;16032 | chr2:178633273;178633272;178633271 | chr2:179498000;179497999;179497998 |
| Novex-1 | 5394 | 16405;16406;16407 | chr2:178633273;178633272;178633271 | chr2:179498000;179497999;179497998 |
| Novex-2 | 5461 | 16606;16607;16608 | chr2:178633273;178633272;178633271 | chr2:179498000;179497999;179497998 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs794729237  |
None | 0.997 | N | 0.558 | 0.22 | 0.213573922156 | gnomAD-4.0.0 | 3.42194E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47464E-04 | 8.99651E-07 | 2.31938E-05 | 0 |
| E/Q | rs776325338 |
-0.127 | 0.999 | N | 0.661 | 0.341 | 0.18995819373 | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.91E-05 | 1.40726E-04 |
| E/Q | rs776325338 |
-0.127 | 0.999 | N | 0.661 | 0.341 | 0.18995819373 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/Q | rs776325338 |
-0.127 | 0.999 | N | 0.661 | 0.341 | 0.18995819373 | gnomAD-4.0.0 | 3.4713E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.66293E-05 | 0 | 1.60185E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.5553 | ambiguous | 0.6151 | pathogenic | -0.843 | Destabilizing | 0.997 | D | 0.734 | deleterious | N | 0.516611345 | None | None | N |
| E/C | 0.9818 | likely_pathogenic | 0.9812 | pathogenic | -0.24 | Destabilizing | 1.0 | D | 0.702 | prob.delet. | None | None | None | None | N |
| E/D | 0.3991 | ambiguous | 0.3591 | ambiguous | -0.765 | Destabilizing | 0.997 | D | 0.558 | neutral | N | 0.429774004 | None | None | N |
| E/F | 0.9736 | likely_pathogenic | 0.9805 | pathogenic | -0.604 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| E/G | 0.4132 | ambiguous | 0.4387 | ambiguous | -1.111 | Destabilizing | 0.999 | D | 0.623 | neutral | N | 0.448627992 | None | None | N |
| E/H | 0.881 | likely_pathogenic | 0.9053 | pathogenic | -0.658 | Destabilizing | 1.0 | D | 0.686 | prob.delet. | None | None | None | None | N |
| E/I | 0.9269 | likely_pathogenic | 0.9524 | pathogenic | -0.143 | Destabilizing | 0.999 | D | 0.694 | prob.delet. | None | None | None | None | N |
| E/K | 0.3666 | ambiguous | 0.5191 | ambiguous | -0.143 | Destabilizing | 0.997 | D | 0.693 | prob.delet. | N | 0.475064041 | None | None | N |
| E/L | 0.9193 | likely_pathogenic | 0.9354 | pathogenic | -0.143 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| E/M | 0.869 | likely_pathogenic | 0.8939 | pathogenic | 0.242 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| E/N | 0.6347 | likely_pathogenic | 0.6665 | pathogenic | -0.555 | Destabilizing | 0.999 | D | 0.706 | prob.delet. | None | None | None | None | N |
| E/P | 0.9896 | likely_pathogenic | 0.9916 | pathogenic | -0.356 | Destabilizing | 0.999 | D | 0.661 | prob.neutral | None | None | None | None | N |
| E/Q | 0.3243 | likely_benign | 0.3771 | ambiguous | -0.499 | Destabilizing | 0.999 | D | 0.661 | prob.neutral | N | 0.454857581 | None | None | N |
| E/R | 0.5956 | likely_pathogenic | 0.7 | pathogenic | 0.066 | Stabilizing | 0.999 | D | 0.703 | prob.delet. | None | None | None | None | N |
| E/S | 0.589 | likely_pathogenic | 0.6152 | pathogenic | -0.758 | Destabilizing | 0.998 | D | 0.706 | prob.delet. | None | None | None | None | N |
| E/T | 0.7268 | likely_pathogenic | 0.7839 | pathogenic | -0.538 | Destabilizing | 0.999 | D | 0.701 | prob.delet. | None | None | None | None | N |
| E/V | 0.794 | likely_pathogenic | 0.8515 | pathogenic | -0.356 | Destabilizing | 0.999 | D | 0.612 | neutral | D | 0.611000455 | None | None | N |
| E/W | 0.9937 | likely_pathogenic | 0.9946 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.701 | prob.delet. | None | None | None | None | N |
| E/Y | 0.951 | likely_pathogenic | 0.9624 | pathogenic | -0.351 | Destabilizing | 1.0 | D | 0.657 | prob.neutral | None | None | None | None | N |
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.