Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23544 | 70855;70856;70857 | chr2:178575502;178575501;178575500 | chr2:179440229;179440228;179440227 |
| N2AB | 21903 | 65932;65933;65934 | chr2:178575502;178575501;178575500 | chr2:179440229;179440228;179440227 |
| N2A | 20976 | 63151;63152;63153 | chr2:178575502;178575501;178575500 | chr2:179440229;179440228;179440227 |
| N2B | 14479 | 43660;43661;43662 | chr2:178575502;178575501;178575500 | chr2:179440229;179440228;179440227 |
| Novex-1 | 14604 | 44035;44036;44037 | chr2:178575502;178575501;178575500 | chr2:179440229;179440228;179440227 |
| Novex-2 | 14671 | 44236;44237;44238 | chr2:178575502;178575501;178575500 | chr2:179440229;179440228;179440227 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.099 | N | 0.271 | 0.109 | 0.388495093706 | gnomAD-4.0.0 | 6.84248E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99541E-07 | 0 | 0 |
| I/V | rs1424128592  |
-1.196 | 0.001 | N | 0.085 | 0.044 | 0.37762505005 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| I/V | rs1424128592 |
-1.196 | 0.001 | N | 0.085 | 0.044 | 0.37762505005 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/V | rs1424128592 |
-1.196 | 0.001 | N | 0.085 | 0.044 | 0.37762505005 | gnomAD-4.0.0 | 4.95789E-06 | None | None | None | None | N | None | 0 | 3.33344E-05 | None | 0 | 0 | None | 0 | 0 | 5.08617E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6121 | likely_pathogenic | 0.5776 | pathogenic | -2.113 | Highly Destabilizing | 0.25 | N | 0.379 | neutral | None | None | None | None | N |
| I/C | 0.7772 | likely_pathogenic | 0.7843 | pathogenic | -2.022 | Highly Destabilizing | 0.977 | D | 0.32 | neutral | None | None | None | None | N |
| I/D | 0.9388 | likely_pathogenic | 0.928 | pathogenic | -2.042 | Highly Destabilizing | 0.85 | D | 0.437 | neutral | None | None | None | None | N |
| I/E | 0.859 | likely_pathogenic | 0.8346 | pathogenic | -1.964 | Destabilizing | 0.85 | D | 0.433 | neutral | None | None | None | None | N |
| I/F | 0.4607 | ambiguous | 0.4216 | ambiguous | -1.539 | Destabilizing | 0.85 | D | 0.362 | neutral | None | None | None | None | N |
| I/G | 0.8973 | likely_pathogenic | 0.8793 | pathogenic | -2.493 | Highly Destabilizing | 0.617 | D | 0.449 | neutral | None | None | None | None | N |
| I/H | 0.8454 | likely_pathogenic | 0.8251 | pathogenic | -1.73 | Destabilizing | 0.992 | D | 0.42 | neutral | None | None | None | None | N |
| I/K | 0.6893 | likely_pathogenic | 0.6507 | pathogenic | -1.486 | Destabilizing | 0.81 | D | 0.437 | neutral | N | 0.495183442 | None | None | N |
| I/L | 0.2666 | likely_benign | 0.2612 | benign | -1.091 | Destabilizing | 0.099 | N | 0.271 | neutral | N | 0.500242545 | None | None | N |
| I/M | 0.1653 | likely_benign | 0.1612 | benign | -1.249 | Destabilizing | 0.81 | D | 0.392 | neutral | N | 0.484881591 | None | None | N |
| I/N | 0.6364 | likely_pathogenic | 0.5761 | pathogenic | -1.538 | Destabilizing | 0.85 | D | 0.462 | neutral | None | None | None | None | N |
| I/P | 0.9613 | likely_pathogenic | 0.9542 | pathogenic | -1.405 | Destabilizing | 0.92 | D | 0.462 | neutral | None | None | None | None | N |
| I/Q | 0.7719 | likely_pathogenic | 0.7426 | pathogenic | -1.672 | Destabilizing | 0.92 | D | 0.455 | neutral | None | None | None | None | N |
| I/R | 0.6316 | likely_pathogenic | 0.5846 | pathogenic | -1.013 | Destabilizing | 0.81 | D | 0.462 | neutral | N | 0.513057126 | None | None | N |
| I/S | 0.5553 | ambiguous | 0.5106 | ambiguous | -2.236 | Highly Destabilizing | 0.447 | N | 0.407 | neutral | None | None | None | None | N |
| I/T | 0.3022 | likely_benign | 0.2799 | benign | -2.029 | Highly Destabilizing | 0.004 | N | 0.178 | neutral | N | 0.491700419 | None | None | N |
| I/V | 0.0768 | likely_benign | 0.0779 | benign | -1.405 | Destabilizing | 0.001 | N | 0.085 | neutral | N | 0.376430686 | None | None | N |
| I/W | 0.9481 | likely_pathogenic | 0.9484 | pathogenic | -1.632 | Destabilizing | 0.992 | D | 0.523 | neutral | None | None | None | None | N |
| I/Y | 0.8196 | likely_pathogenic | 0.7931 | pathogenic | -1.369 | Destabilizing | 0.92 | D | 0.349 | 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.