Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2079 | 6460;6461;6462 | chr2:178775629;178775628;178775627 | chr2:179640356;179640355;179640354 |
| N2AB | 2079 | 6460;6461;6462 | chr2:178775629;178775628;178775627 | chr2:179640356;179640355;179640354 |
| N2A | 2079 | 6460;6461;6462 | chr2:178775629;178775628;178775627 | chr2:179640356;179640355;179640354 |
| N2B | 2033 | 6322;6323;6324 | chr2:178775629;178775628;178775627 | chr2:179640356;179640355;179640354 |
| Novex-1 | 2033 | 6322;6323;6324 | chr2:178775629;178775628;178775627 | chr2:179640356;179640355;179640354 |
| Novex-2 | 2033 | 6322;6323;6324 | chr2:178775629;178775628;178775627 | chr2:179640356;179640355;179640354 |
| Novex-3 | 2079 | 6460;6461;6462 | chr2:178775629;178775628;178775627 | chr2:179640356;179640355;179640354 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.989 | N | 0.508 | 0.394 | 0.494299846589 | gnomAD-4.0.0 | 1.59057E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85651E-06 | 0 | 0 |
| K/R | rs1395240027  |
-0.066 | 0.217 | N | 0.185 | 0.251 | 0.353761421236 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 1.17924E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/R | rs1395240027 |
-0.066 | 0.217 | N | 0.185 | 0.251 | 0.353761421236 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs1395240027 |
-0.066 | 0.217 | N | 0.185 | 0.251 | 0.353761421236 | gnomAD-4.0.0 | 6.57013E-06 | None | None | None | None | I | None | 0 | 6.54707E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.8987 | likely_pathogenic | 0.8573 | pathogenic | -0.278 | Destabilizing | 0.996 | D | 0.559 | neutral | None | None | None | None | I |
| K/C | 0.9588 | likely_pathogenic | 0.9486 | pathogenic | -0.578 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| K/D | 0.9862 | likely_pathogenic | 0.9786 | pathogenic | -0.087 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | I |
| K/E | 0.8173 | likely_pathogenic | 0.7429 | pathogenic | -0.002 | Destabilizing | 0.989 | D | 0.508 | neutral | N | 0.461583147 | None | None | I |
| K/F | 0.9856 | likely_pathogenic | 0.9821 | pathogenic | -0.224 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| K/G | 0.9633 | likely_pathogenic | 0.9436 | pathogenic | -0.546 | Destabilizing | 0.999 | D | 0.568 | neutral | None | None | None | None | I |
| K/H | 0.7236 | likely_pathogenic | 0.6759 | pathogenic | -0.596 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| K/I | 0.8115 | likely_pathogenic | 0.7896 | pathogenic | 0.383 | Stabilizing | 0.999 | D | 0.704 | prob.neutral | N | 0.494114603 | None | None | I |
| K/L | 0.8345 | likely_pathogenic | 0.8058 | pathogenic | 0.383 | Stabilizing | 0.999 | D | 0.568 | neutral | None | None | None | None | I |
| K/M | 0.7713 | likely_pathogenic | 0.7229 | pathogenic | -0.137 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | I |
| K/N | 0.9563 | likely_pathogenic | 0.9305 | pathogenic | -0.278 | Destabilizing | 0.998 | D | 0.639 | neutral | N | 0.513099604 | None | None | I |
| K/P | 0.9959 | likely_pathogenic | 0.9937 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | I |
| K/Q | 0.4885 | ambiguous | 0.4095 | ambiguous | -0.278 | Destabilizing | 0.997 | D | 0.633 | neutral | N | 0.463118214 | None | None | I |
| K/R | 0.114 | likely_benign | 0.1034 | benign | -0.167 | Destabilizing | 0.217 | N | 0.185 | neutral | N | 0.443703351 | None | None | I |
| K/S | 0.9434 | likely_pathogenic | 0.9159 | pathogenic | -0.756 | Destabilizing | 0.996 | D | 0.589 | neutral | None | None | None | None | I |
| K/T | 0.7307 | likely_pathogenic | 0.6755 | pathogenic | -0.489 | Destabilizing | 0.998 | D | 0.639 | neutral | N | 0.492997636 | None | None | I |
| K/V | 0.6927 | likely_pathogenic | 0.6732 | pathogenic | 0.191 | Stabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | I |
| K/W | 0.9848 | likely_pathogenic | 0.9819 | pathogenic | -0.252 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| K/Y | 0.9669 | likely_pathogenic | 0.9608 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
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.