Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29114 | 87565;87566;87567 | chr2:178558014;178558013;178558012 | chr2:179422741;179422740;179422739 |
| N2AB | 27473 | 82642;82643;82644 | chr2:178558014;178558013;178558012 | chr2:179422741;179422740;179422739 |
| N2A | 26546 | 79861;79862;79863 | chr2:178558014;178558013;178558012 | chr2:179422741;179422740;179422739 |
| N2B | 20049 | 60370;60371;60372 | chr2:178558014;178558013;178558012 | chr2:179422741;179422740;179422739 |
| Novex-1 | 20174 | 60745;60746;60747 | chr2:178558014;178558013;178558012 | chr2:179422741;179422740;179422739 |
| Novex-2 | 20241 | 60946;60947;60948 | chr2:178558014;178558013;178558012 | chr2:179422741;179422740;179422739 |
| 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/K | rs1253866874  |
-1.277 | None | N | 0.151 | 0.095 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/K | rs1253866874 |
-1.277 | None | N | 0.151 | 0.095 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/K | rs1253866874 |
-1.277 | None | N | 0.151 | 0.095 | None | gnomAD-4.0.0 | 1.11547E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.35612E-05 | 0 | 3.20205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2575 | likely_benign | 0.2248 | benign | -0.605 | Destabilizing | 0.035 | N | 0.488 | neutral | None | None | None | None | I |
| R/C | 0.1396 | likely_benign | 0.1125 | benign | -0.649 | Destabilizing | 0.935 | D | 0.636 | neutral | None | None | None | None | I |
| R/D | 0.5354 | ambiguous | 0.4816 | ambiguous | 0.066 | Stabilizing | 0.149 | N | 0.587 | neutral | None | None | None | None | I |
| R/E | 0.2621 | likely_benign | 0.2312 | benign | 0.205 | Stabilizing | 0.035 | N | 0.464 | neutral | None | None | None | None | I |
| R/F | 0.3762 | ambiguous | 0.316 | benign | -0.393 | Destabilizing | 0.791 | D | 0.621 | neutral | None | None | None | None | I |
| R/G | 0.2052 | likely_benign | 0.1815 | benign | -0.915 | Destabilizing | 0.117 | N | 0.545 | neutral | D | 0.535598417 | None | None | I |
| R/H | 0.0919 | likely_benign | 0.0767 | benign | -1.245 | Destabilizing | 0.555 | D | 0.513 | neutral | None | None | None | None | I |
| R/I | 0.1468 | likely_benign | 0.1444 | benign | 0.226 | Stabilizing | 0.484 | N | 0.625 | neutral | N | 0.45149974 | None | None | I |
| R/K | 0.0692 | likely_benign | 0.07 | benign | -0.546 | Destabilizing | None | N | 0.151 | neutral | N | 0.418443172 | None | None | I |
| R/L | 0.1577 | likely_benign | 0.1421 | benign | 0.226 | Stabilizing | 0.149 | N | 0.545 | neutral | None | None | None | None | I |
| R/M | 0.1588 | likely_benign | 0.1531 | benign | -0.286 | Destabilizing | 0.791 | D | 0.577 | neutral | None | None | None | None | I |
| R/N | 0.3459 | ambiguous | 0.2927 | benign | -0.217 | Destabilizing | 0.149 | N | 0.475 | neutral | None | None | None | None | I |
| R/P | 0.4436 | ambiguous | 0.3912 | ambiguous | -0.03 | Destabilizing | 0.555 | D | 0.613 | neutral | None | None | None | None | I |
| R/Q | 0.087 | likely_benign | 0.0793 | benign | -0.284 | Destabilizing | 0.081 | N | 0.501 | neutral | None | None | None | None | I |
| R/S | 0.3055 | likely_benign | 0.2586 | benign | -0.9 | Destabilizing | 0.062 | N | 0.489 | neutral | N | 0.485822958 | None | None | I |
| R/T | 0.1356 | likely_benign | 0.1266 | benign | -0.572 | Destabilizing | 0.117 | N | 0.529 | neutral | N | 0.465429043 | None | None | I |
| R/V | 0.2053 | likely_benign | 0.1861 | benign | -0.03 | Destabilizing | 0.38 | N | 0.584 | neutral | None | None | None | None | I |
| R/W | 0.1571 | likely_benign | 0.1313 | benign | -0.123 | Destabilizing | 0.935 | D | 0.657 | neutral | None | None | None | None | I |
| R/Y | 0.2726 | likely_benign | 0.2172 | benign | 0.175 | Stabilizing | 0.791 | D | 0.629 | 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.