Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1374 | 4345;4346;4347 | chr2:178778962;178778961;178778960 | chr2:179643689;179643688;179643687 |
| N2AB | 1374 | 4345;4346;4347 | chr2:178778962;178778961;178778960 | chr2:179643689;179643688;179643687 |
| N2A | 1374 | 4345;4346;4347 | chr2:178778962;178778961;178778960 | chr2:179643689;179643688;179643687 |
| N2B | 1328 | 4207;4208;4209 | chr2:178778962;178778961;178778960 | chr2:179643689;179643688;179643687 |
| Novex-1 | 1328 | 4207;4208;4209 | chr2:178778962;178778961;178778960 | chr2:179643689;179643688;179643687 |
| Novex-2 | 1328 | 4207;4208;4209 | chr2:178778962;178778961;178778960 | chr2:179643689;179643688;179643687 |
| Novex-3 | 1374 | 4345;4346;4347 | chr2:178778962;178778961;178778960 | chr2:179643689;179643688;179643687 |
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/L | rs770961696  |
-0.227 | 0.689 | N | 0.353 | 0.247 | 0.542587012665 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| I/L | rs770961696 |
-0.227 | 0.689 | N | 0.353 | 0.247 | 0.542587012665 | gnomAD-4.0.0 | 1.59085E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85704E-06 | 0 | 0 |
| I/V | rs770961696 |
-0.465 | 0.122 | N | 0.219 | 0.166 | 0.620545251997 | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | I | None | 1.23077E-04 | 0 | None | 0 | 1.09146E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs770961696 |
-0.465 | 0.122 | N | 0.219 | 0.166 | 0.620545251997 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92678E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs770961696 |
-0.465 | 0.122 | N | 0.219 | 0.166 | 0.620545251997 | gnomAD-4.0.0 | 3.84185E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.85319E-05 | None | 0 | 0 | 0 | 1.34012E-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 | 0.943 | likely_pathogenic | 0.9122 | pathogenic | -1.169 | Destabilizing | 0.931 | D | 0.568 | neutral | None | None | None | None | I |
| I/C | 0.9905 | likely_pathogenic | 0.9867 | pathogenic | -0.744 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| I/D | 0.9991 | likely_pathogenic | 0.9982 | pathogenic | -0.137 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | I |
| I/E | 0.9961 | likely_pathogenic | 0.9938 | pathogenic | -0.114 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| I/F | 0.8487 | likely_pathogenic | 0.804 | pathogenic | -0.669 | Destabilizing | 0.994 | D | 0.503 | neutral | N | 0.451997449 | None | None | I |
| I/G | 0.9968 | likely_pathogenic | 0.9947 | pathogenic | -1.475 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | I |
| I/H | 0.9965 | likely_pathogenic | 0.994 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| I/K | 0.9926 | likely_pathogenic | 0.9877 | pathogenic | -0.568 | Destabilizing | 0.999 | D | 0.68 | prob.neutral | None | None | None | None | I |
| I/L | 0.5518 | ambiguous | 0.5033 | ambiguous | -0.412 | Destabilizing | 0.689 | D | 0.353 | neutral | N | 0.456063346 | None | None | I |
| I/M | 0.6732 | likely_pathogenic | 0.6228 | pathogenic | -0.5 | Destabilizing | 0.994 | D | 0.528 | neutral | N | 0.486100735 | None | None | I |
| I/N | 0.9893 | likely_pathogenic | 0.9825 | pathogenic | -0.494 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | N | 0.437780413 | None | None | I |
| I/P | 0.9966 | likely_pathogenic | 0.9939 | pathogenic | -0.632 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | I |
| I/Q | 0.9937 | likely_pathogenic | 0.9895 | pathogenic | -0.572 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | I |
| I/R | 0.9856 | likely_pathogenic | 0.9768 | pathogenic | -0.119 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | I |
| I/S | 0.9703 | likely_pathogenic | 0.953 | pathogenic | -1.15 | Destabilizing | 0.994 | D | 0.638 | neutral | N | 0.300085524 | None | None | I |
| I/T | 0.9527 | likely_pathogenic | 0.9324 | pathogenic | -0.997 | Destabilizing | 0.961 | D | 0.537 | neutral | N | 0.366955689 | None | None | I |
| I/V | 0.1821 | likely_benign | 0.1755 | benign | -0.632 | Destabilizing | 0.122 | N | 0.219 | neutral | N | 0.430323848 | None | None | I |
| I/W | 0.9966 | likely_pathogenic | 0.9946 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| I/Y | 0.9846 | likely_pathogenic | 0.9739 | pathogenic | -0.472 | Destabilizing | 0.999 | D | 0.662 | 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.