Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2130 | 6613;6614;6615 | chr2:178775476;178775475;178775474 | chr2:179640203;179640202;179640201 |
| N2AB | 2130 | 6613;6614;6615 | chr2:178775476;178775475;178775474 | chr2:179640203;179640202;179640201 |
| N2A | 2130 | 6613;6614;6615 | chr2:178775476;178775475;178775474 | chr2:179640203;179640202;179640201 |
| N2B | 2084 | 6475;6476;6477 | chr2:178775476;178775475;178775474 | chr2:179640203;179640202;179640201 |
| Novex-1 | 2084 | 6475;6476;6477 | chr2:178775476;178775475;178775474 | chr2:179640203;179640202;179640201 |
| Novex-2 | 2084 | 6475;6476;6477 | chr2:178775476;178775475;178775474 | chr2:179640203;179640202;179640201 |
| Novex-3 | 2130 | 6613;6614;6615 | chr2:178775476;178775475;178775474 | chr2:179640203;179640202;179640201 |
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/K | rs762914675  |
-0.316 | 1.0 | D | 0.578 | 0.529 | None | gnomAD-2.1.1 | 4.38E-05 | None | None | None | None | N | None | 0 | 8.69E-05 | None | 0 | 5.46E-05 | None | 1.30668E-04 | None | 0 | 2.64E-05 | 0 |
| E/K | rs762914675 |
-0.316 | 1.0 | D | 0.578 | 0.529 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs762914675 |
-0.316 | 1.0 | D | 0.578 | 0.529 | None | gnomAD-4.0.0 | 1.92087E-05 | None | None | None | None | N | None | 1.33518E-05 | 5.003E-05 | None | 0 | 4.4611E-05 | None | 0 | 0 | 1.18645E-05 | 9.88121E-05 | 3.20102E-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 | 0.4624 | ambiguous | 0.5249 | ambiguous | -0.717 | Destabilizing | 0.999 | D | 0.562 | neutral | D | 0.595132379 | None | None | N |
| E/C | 0.9862 | likely_pathogenic | 0.9879 | pathogenic | -0.347 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| E/D | 0.3843 | ambiguous | 0.4414 | ambiguous | -0.859 | Destabilizing | 0.999 | D | 0.457 | neutral | N | 0.508491427 | None | None | N |
| E/F | 0.9738 | likely_pathogenic | 0.9801 | pathogenic | -0.379 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| E/G | 0.5514 | ambiguous | 0.6104 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.537 | neutral | D | 0.529126904 | None | None | N |
| E/H | 0.8968 | likely_pathogenic | 0.9222 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| E/I | 0.8524 | likely_pathogenic | 0.8794 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| E/K | 0.5558 | ambiguous | 0.626 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.578 | neutral | D | 0.565730694 | None | None | N |
| E/L | 0.8645 | likely_pathogenic | 0.8909 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| E/M | 0.8684 | likely_pathogenic | 0.8946 | pathogenic | 0.269 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| E/N | 0.7512 | likely_pathogenic | 0.8066 | pathogenic | -0.682 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| E/P | 0.9749 | likely_pathogenic | 0.9798 | pathogenic | -0.204 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | N |
| E/Q | 0.4172 | ambiguous | 0.4821 | ambiguous | -0.618 | Destabilizing | 1.0 | D | 0.567 | neutral | D | 0.536699056 | None | None | N |
| E/R | 0.6946 | likely_pathogenic | 0.7498 | pathogenic | 0.026 | Stabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| E/S | 0.5634 | ambiguous | 0.6247 | pathogenic | -0.889 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| E/T | 0.6682 | likely_pathogenic | 0.7205 | pathogenic | -0.667 | Destabilizing | 1.0 | D | 0.59 | neutral | None | None | None | None | N |
| E/V | 0.6464 | likely_pathogenic | 0.693 | pathogenic | -0.204 | Destabilizing | 1.0 | D | 0.592 | neutral | D | 0.627576918 | None | None | N |
| E/W | 0.9919 | likely_pathogenic | 0.9939 | pathogenic | -0.157 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| E/Y | 0.9564 | likely_pathogenic | 0.9679 | pathogenic | -0.137 | Destabilizing | 1.0 | D | 0.64 | 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.