Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32463 | 97612;97613;97614 | chr2:178542369;178542368;178542367 | chr2:179407096;179407095;179407094 |
| N2AB | 30822 | 92689;92690;92691 | chr2:178542369;178542368;178542367 | chr2:179407096;179407095;179407094 |
| N2A | 29895 | 89908;89909;89910 | chr2:178542369;178542368;178542367 | chr2:179407096;179407095;179407094 |
| N2B | 23398 | 70417;70418;70419 | chr2:178542369;178542368;178542367 | chr2:179407096;179407095;179407094 |
| Novex-1 | 23523 | 70792;70793;70794 | chr2:178542369;178542368;178542367 | chr2:179407096;179407095;179407094 |
| Novex-2 | 23590 | 70993;70994;70995 | chr2:178542369;178542368;178542367 | chr2:179407096;179407095;179407094 |
| 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 | rs1398002611  |
-0.055 | 0.896 | N | 0.481 | 0.196 | 0.263612267334 | gnomAD-2.1.1 | 9.56E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.94578E-04 | 0 |
| R/G | rs1398002611 |
-0.055 | 0.896 | N | 0.481 | 0.196 | 0.263612267334 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/G | rs1398002611 |
-0.055 | 0.896 | N | 0.481 | 0.196 | 0.263612267334 | gnomAD-4.0.0 | 5.12568E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57391E-06 | 0 | 0 |
| R/K | rs1257117887 |
-0.073 | 0.011 | N | 0.215 | 0.115 | 0.104622674875 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/K | rs1257117887 |
-0.073 | 0.011 | N | 0.215 | 0.115 | 0.104622674875 | gnomAD-4.0.0 | 3.18322E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71755E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5925 | likely_pathogenic | 0.5766 | pathogenic | -0.048 | Destabilizing | 0.919 | D | 0.473 | neutral | None | None | None | None | N |
| R/C | 0.3131 | likely_benign | 0.2742 | benign | -0.308 | Destabilizing | 0.999 | D | 0.62 | neutral | None | None | None | None | N |
| R/D | 0.7687 | likely_pathogenic | 0.7712 | pathogenic | -0.251 | Destabilizing | 0.976 | D | 0.489 | neutral | None | None | None | None | N |
| R/E | 0.6326 | likely_pathogenic | 0.6102 | pathogenic | -0.212 | Destabilizing | 0.851 | D | 0.494 | neutral | None | None | None | None | N |
| R/F | 0.785 | likely_pathogenic | 0.7636 | pathogenic | -0.368 | Destabilizing | 0.996 | D | 0.599 | neutral | None | None | None | None | N |
| R/G | 0.326 | likely_benign | 0.3034 | benign | -0.189 | Destabilizing | 0.896 | D | 0.481 | neutral | N | 0.398786605 | None | None | N |
| R/H | 0.1424 | likely_benign | 0.1341 | benign | -0.61 | Destabilizing | 0.996 | D | 0.522 | neutral | None | None | None | None | N |
| R/I | 0.6757 | likely_pathogenic | 0.6655 | pathogenic | 0.277 | Stabilizing | 0.984 | D | 0.597 | neutral | N | 0.469224012 | None | None | N |
| R/K | 0.1579 | likely_benign | 0.1534 | benign | -0.208 | Destabilizing | 0.011 | N | 0.215 | neutral | N | 0.402237916 | None | None | N |
| R/L | 0.482 | ambiguous | 0.4576 | ambiguous | 0.277 | Stabilizing | 0.919 | D | 0.481 | neutral | None | None | None | None | N |
| R/M | 0.5555 | ambiguous | 0.5523 | ambiguous | -0.1 | Destabilizing | 0.999 | D | 0.499 | neutral | None | None | None | None | N |
| R/N | 0.6193 | likely_pathogenic | 0.618 | pathogenic | -0.084 | Destabilizing | 0.976 | D | 0.491 | neutral | None | None | None | None | N |
| R/P | 0.849 | likely_pathogenic | 0.8407 | pathogenic | 0.186 | Stabilizing | 0.988 | D | 0.543 | neutral | None | None | None | None | N |
| R/Q | 0.1787 | likely_benign | 0.1634 | benign | -0.157 | Destabilizing | 0.976 | D | 0.526 | neutral | None | None | None | None | N |
| R/S | 0.6222 | likely_pathogenic | 0.6166 | pathogenic | -0.337 | Destabilizing | 0.896 | D | 0.497 | neutral | N | 0.489163467 | None | None | N |
| R/T | 0.5379 | ambiguous | 0.5444 | ambiguous | -0.189 | Destabilizing | 0.896 | D | 0.469 | neutral | N | 0.456853749 | None | None | N |
| R/V | 0.6895 | likely_pathogenic | 0.6749 | pathogenic | 0.186 | Stabilizing | 0.988 | D | 0.567 | neutral | None | None | None | None | N |
| R/W | 0.3888 | ambiguous | 0.3413 | ambiguous | -0.508 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| R/Y | 0.5634 | ambiguous | 0.5249 | ambiguous | -0.106 | Destabilizing | 0.996 | D | 0.548 | 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.