Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32479 | 97660;97661;97662 | chr2:178542321;178542320;178542319 | chr2:179407048;179407047;179407046 |
| N2AB | 30838 | 92737;92738;92739 | chr2:178542321;178542320;178542319 | chr2:179407048;179407047;179407046 |
| N2A | 29911 | 89956;89957;89958 | chr2:178542321;178542320;178542319 | chr2:179407048;179407047;179407046 |
| N2B | 23414 | 70465;70466;70467 | chr2:178542321;178542320;178542319 | chr2:179407048;179407047;179407046 |
| Novex-1 | 23539 | 70840;70841;70842 | chr2:178542321;178542320;178542319 | chr2:179407048;179407047;179407046 |
| Novex-2 | 23606 | 71041;71042;71043 | chr2:178542321;178542320;178542319 | chr2:179407048;179407047;179407046 |
| 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/C | rs200148139  |
-0.281 | 1.0 | N | 0.747 | 0.483 | 0.771612649732 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/C | rs200148139 |
-0.281 | 1.0 | N | 0.747 | 0.483 | 0.771612649732 | gnomAD-4.0.0 | 4.79196E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29805E-06 | 0 | 0 |
| R/H | rs369845358 |
-1.108 | 1.0 | N | 0.712 | 0.436 | None | gnomAD-2.1.1 | 6.11E-05 | None | None | None | None | I | None | 5.41983E-04 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 1.41363E-04 |
| R/H | rs369845358 |
-1.108 | 1.0 | N | 0.712 | 0.436 | None | gnomAD-3.1.2 | 1.31492E-04 | None | None | None | None | I | None | 4.34447E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs369845358 |
-1.108 | 1.0 | N | 0.712 | 0.436 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs369845358 |
-1.108 | 1.0 | N | 0.712 | 0.436 | None | gnomAD-4.0.0 | 3.53409E-05 | None | None | None | None | I | None | 3.73363E-04 | 1.00157E-04 | None | 0 | 4.47427E-05 | None | 0 | 0 | 1.44137E-05 | 1.10001E-05 | 4.80492E-05 |
| R/S | rs200148139 |
-0.345 | 1.0 | N | 0.634 | 0.414 | 0.44551302605 | gnomAD-2.1.1 | 1.3639E-04 | None | None | None | None | I | None | 0 | 0 | None | 3.29969E-03 | 0 | None | 0 | None | 0 | 1.57E-05 | 2.82167E-04 |
| R/S | rs200148139 |
-0.345 | 1.0 | N | 0.634 | 0.414 | 0.44551302605 | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 3.74424E-03 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs200148139 |
-0.345 | 1.0 | N | 0.634 | 0.414 | 0.44551302605 | gnomAD-4.0.0 | 9.54818E-05 | None | None | None | None | I | None | 0 | 0 | None | 3.98864E-03 | 0 | None | 0 | 0 | 1.95005E-05 | 0 | 2.0824E-04 |
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 | 0.9842 | likely_pathogenic | 0.9754 | pathogenic | -0.024 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | I |
| R/C | 0.9081 | likely_pathogenic | 0.8614 | pathogenic | -0.208 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.506691922 | None | None | I |
| R/D | 0.9931 | likely_pathogenic | 0.9908 | pathogenic | -0.121 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| R/E | 0.9781 | likely_pathogenic | 0.9702 | pathogenic | -0.034 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | I |
| R/F | 0.9896 | likely_pathogenic | 0.9854 | pathogenic | -0.209 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| R/G | 0.978 | likely_pathogenic | 0.9648 | pathogenic | -0.238 | Destabilizing | 1.0 | D | 0.575 | neutral | N | 0.475196083 | None | None | I |
| R/H | 0.7441 | likely_pathogenic | 0.6632 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.488080688 | None | None | I |
| R/I | 0.9394 | likely_pathogenic | 0.9196 | pathogenic | 0.508 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| R/K | 0.6863 | likely_pathogenic | 0.5997 | pathogenic | -0.082 | Destabilizing | 0.998 | D | 0.418 | neutral | None | None | None | None | I |
| R/L | 0.9316 | likely_pathogenic | 0.9029 | pathogenic | 0.508 | Stabilizing | 1.0 | D | 0.575 | neutral | N | 0.521732538 | None | None | I |
| R/M | 0.9765 | likely_pathogenic | 0.9646 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| R/N | 0.9861 | likely_pathogenic | 0.9796 | pathogenic | 0.042 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| R/P | 0.9762 | likely_pathogenic | 0.9717 | pathogenic | 0.352 | Stabilizing | 1.0 | D | 0.666 | neutral | N | 0.46776116 | None | None | I |
| R/Q | 0.777 | likely_pathogenic | 0.6996 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/S | 0.9863 | likely_pathogenic | 0.979 | pathogenic | -0.258 | Destabilizing | 1.0 | D | 0.634 | neutral | N | 0.490889556 | None | None | I |
| R/T | 0.9784 | likely_pathogenic | 0.9677 | pathogenic | -0.022 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | I |
| R/V | 0.9661 | likely_pathogenic | 0.9545 | pathogenic | 0.352 | Stabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| R/W | 0.9074 | likely_pathogenic | 0.8706 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| R/Y | 0.9543 | likely_pathogenic | 0.9384 | pathogenic | 0.122 | Stabilizing | 1.0 | D | 0.699 | prob.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.