Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28644 | 86155;86156;86157 | chr2:178560202;178560201;178560200 | chr2:179424929;179424928;179424927 |
| N2AB | 27003 | 81232;81233;81234 | chr2:178560202;178560201;178560200 | chr2:179424929;179424928;179424927 |
| N2A | 26076 | 78451;78452;78453 | chr2:178560202;178560201;178560200 | chr2:179424929;179424928;179424927 |
| N2B | 19579 | 58960;58961;58962 | chr2:178560202;178560201;178560200 | chr2:179424929;179424928;179424927 |
| Novex-1 | 19704 | 59335;59336;59337 | chr2:178560202;178560201;178560200 | chr2:179424929;179424928;179424927 |
| Novex-2 | 19771 | 59536;59537;59538 | chr2:178560202;178560201;178560200 | chr2:179424929;179424928;179424927 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.361 | N | 0.549 | 0.194 | 0.290962096972 | gnomAD-4.0.0 | 9.60257E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.05E-05 | 0 | 0 |
| R/S | rs1322931412  |
-0.913 | 0.22 | N | 0.484 | 0.147 | 0.101711395817 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/S | rs1322931412 |
-0.913 | 0.22 | N | 0.484 | 0.147 | 0.101711395817 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/S | rs1322931412 |
-0.913 | 0.22 | N | 0.484 | 0.147 | 0.101711395817 | gnomAD-4.0.0 | 6.40669E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19661E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2834 | likely_benign | 0.2758 | benign | -0.462 | Destabilizing | 0.134 | N | 0.445 | neutral | None | None | None | None | N |
| R/C | 0.1291 | likely_benign | 0.1257 | benign | -0.477 | Destabilizing | 0.984 | D | 0.569 | neutral | None | None | None | None | N |
| R/D | 0.6769 | likely_pathogenic | 0.6769 | pathogenic | -0.054 | Destabilizing | 0.428 | N | 0.565 | neutral | None | None | None | None | N |
| R/E | 0.3572 | ambiguous | 0.3505 | ambiguous | 0.043 | Stabilizing | 0.134 | N | 0.423 | neutral | None | None | None | None | N |
| R/F | 0.3765 | ambiguous | 0.3583 | ambiguous | -0.445 | Destabilizing | 0.942 | D | 0.556 | neutral | None | None | None | None | N |
| R/G | 0.2679 | likely_benign | 0.2582 | benign | -0.733 | Destabilizing | 0.361 | N | 0.549 | neutral | N | 0.475262216 | None | None | N |
| R/H | 0.0892 | likely_benign | 0.0848 | benign | -1.092 | Destabilizing | 0.842 | D | 0.477 | neutral | None | None | None | None | N |
| R/I | 0.1877 | likely_benign | 0.1744 | benign | 0.243 | Stabilizing | 0.842 | D | 0.603 | neutral | None | None | None | None | N |
| R/K | 0.0742 | likely_benign | 0.073 | benign | -0.543 | Destabilizing | None | N | 0.137 | neutral | N | 0.371848799 | None | None | N |
| R/L | 0.1576 | likely_benign | 0.1558 | benign | 0.243 | Stabilizing | 0.428 | N | 0.549 | neutral | None | None | None | None | N |
| R/M | 0.1916 | likely_benign | 0.1884 | benign | -0.116 | Destabilizing | 0.8 | D | 0.534 | neutral | N | 0.448885431 | None | None | N |
| R/N | 0.5006 | ambiguous | 0.4942 | ambiguous | -0.086 | Destabilizing | 0.428 | N | 0.411 | neutral | None | None | None | None | N |
| R/P | 0.412 | ambiguous | 0.4102 | ambiguous | 0.029 | Stabilizing | 0.842 | D | 0.556 | neutral | None | None | None | None | N |
| R/Q | 0.1006 | likely_benign | 0.0981 | benign | -0.251 | Destabilizing | 0.01 | N | 0.271 | neutral | None | None | None | None | N |
| R/S | 0.4098 | ambiguous | 0.3991 | ambiguous | -0.699 | Destabilizing | 0.22 | N | 0.484 | neutral | N | 0.476360033 | None | None | N |
| R/T | 0.1749 | likely_benign | 0.1748 | benign | -0.439 | Destabilizing | 0.361 | N | 0.465 | neutral | N | 0.401501623 | None | None | N |
| R/V | 0.2322 | likely_benign | 0.2221 | benign | 0.029 | Stabilizing | 0.428 | N | 0.621 | neutral | None | None | None | None | N |
| R/W | 0.1459 | likely_benign | 0.1546 | benign | -0.238 | Destabilizing | 0.979 | D | 0.591 | neutral | N | 0.46441289 | None | None | N |
| R/Y | 0.2971 | likely_benign | 0.2913 | benign | 0.092 | Stabilizing | 0.842 | D | 0.58 | 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.