Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23813 | 71662;71663;71664 | chr2:178574695;178574694;178574693 | chr2:179439422;179439421;179439420 |
| N2AB | 22172 | 66739;66740;66741 | chr2:178574695;178574694;178574693 | chr2:179439422;179439421;179439420 |
| N2A | 21245 | 63958;63959;63960 | chr2:178574695;178574694;178574693 | chr2:179439422;179439421;179439420 |
| N2B | 14748 | 44467;44468;44469 | chr2:178574695;178574694;178574693 | chr2:179439422;179439421;179439420 |
| Novex-1 | 14873 | 44842;44843;44844 | chr2:178574695;178574694;178574693 | chr2:179439422;179439421;179439420 |
| Novex-2 | 14940 | 45043;45044;45045 | chr2:178574695;178574694;178574693 | chr2:179439422;179439421;179439420 |
| 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/T | rs1304761942  |
-0.838 | 0.546 | N | 0.483 | 0.32 | 0.642158408529 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1304761942 |
-0.838 | 0.546 | N | 0.483 | 0.32 | 0.642158408529 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| I/T | rs1304761942 |
-0.838 | 0.546 | N | 0.483 | 0.32 | 0.642158408529 | gnomAD-4.0.0 | 3.84578E-06 | None | None | None | None | N | None | 0 | 1.69578E-05 | None | 0 | 0 | None | 0 | 0 | 2.39437E-06 | 1.34124E-05 | 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 | 0.5364 | ambiguous | 0.4986 | ambiguous | -1.988 | Destabilizing | 0.248 | N | 0.556 | neutral | None | None | None | None | N |
| I/C | 0.6675 | likely_pathogenic | 0.6498 | pathogenic | -1.366 | Destabilizing | 0.977 | D | 0.597 | neutral | None | None | None | None | N |
| I/D | 0.8957 | likely_pathogenic | 0.8921 | pathogenic | -1.323 | Destabilizing | 0.972 | D | 0.693 | prob.delet. | None | None | None | None | N |
| I/E | 0.7865 | likely_pathogenic | 0.7831 | pathogenic | -1.255 | Destabilizing | 0.919 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/F | 0.3355 | likely_benign | 0.3321 | benign | -1.241 | Destabilizing | 0.808 | D | 0.48 | neutral | N | 0.481916894 | None | None | N |
| I/G | 0.8216 | likely_pathogenic | 0.8037 | pathogenic | -2.386 | Highly Destabilizing | 0.919 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/H | 0.7556 | likely_pathogenic | 0.7419 | pathogenic | -1.552 | Destabilizing | 0.992 | D | 0.701 | prob.delet. | None | None | None | None | N |
| I/K | 0.6005 | likely_pathogenic | 0.5527 | ambiguous | -1.388 | Destabilizing | 0.919 | D | 0.671 | prob.neutral | None | None | None | None | N |
| I/L | 0.0845 | likely_benign | 0.0814 | benign | -0.928 | Destabilizing | 0.002 | N | 0.276 | neutral | N | 0.378807349 | None | None | N |
| I/M | 0.1126 | likely_benign | 0.1107 | benign | -0.838 | Destabilizing | 0.808 | D | 0.533 | neutral | D | 0.530939172 | None | None | N |
| I/N | 0.494 | ambiguous | 0.48 | ambiguous | -1.296 | Destabilizing | 0.963 | D | 0.699 | prob.delet. | N | 0.489678801 | None | None | N |
| I/P | 0.9556 | likely_pathogenic | 0.9615 | pathogenic | -1.252 | Destabilizing | 0.972 | D | 0.697 | prob.delet. | None | None | None | None | N |
| I/Q | 0.6323 | likely_pathogenic | 0.606 | pathogenic | -1.392 | Destabilizing | 0.972 | D | 0.703 | prob.delet. | None | None | None | None | N |
| I/R | 0.5769 | likely_pathogenic | 0.5288 | ambiguous | -0.876 | Destabilizing | 0.919 | D | 0.7 | prob.delet. | None | None | None | None | N |
| I/S | 0.5394 | ambiguous | 0.5135 | ambiguous | -2.027 | Highly Destabilizing | 0.808 | D | 0.612 | neutral | N | 0.383327734 | None | None | N |
| I/T | 0.385 | ambiguous | 0.393 | ambiguous | -1.832 | Destabilizing | 0.546 | D | 0.483 | neutral | N | 0.490937989 | None | None | N |
| I/V | 0.0941 | likely_benign | 0.0877 | benign | -1.252 | Destabilizing | 0.002 | N | 0.208 | neutral | N | 0.466039544 | None | None | N |
| I/W | 0.9292 | likely_pathogenic | 0.9293 | pathogenic | -1.34 | Destabilizing | 0.992 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7327 | likely_pathogenic | 0.7451 | pathogenic | -1.118 | Destabilizing | 0.919 | D | 0.566 | 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.