Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27989 | 84190;84191;84192 | chr2:178562167;178562166;178562165 | chr2:179426894;179426893;179426892 |
| N2AB | 26348 | 79267;79268;79269 | chr2:178562167;178562166;178562165 | chr2:179426894;179426893;179426892 |
| N2A | 25421 | 76486;76487;76488 | chr2:178562167;178562166;178562165 | chr2:179426894;179426893;179426892 |
| N2B | 18924 | 56995;56996;56997 | chr2:178562167;178562166;178562165 | chr2:179426894;179426893;179426892 |
| Novex-1 | 19049 | 57370;57371;57372 | chr2:178562167;178562166;178562165 | chr2:179426894;179426893;179426892 |
| Novex-2 | 19116 | 57571;57572;57573 | chr2:178562167;178562166;178562165 | chr2:179426894;179426893;179426892 |
| 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 | rs1419715288  |
0.265 | 0.944 | N | 0.495 | 0.235 | 0.394230963961 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| R/K | rs1419715288 |
0.265 | 0.944 | N | 0.495 | 0.235 | 0.394230963961 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs1419715288 |
0.265 | 0.944 | N | 0.495 | 0.235 | 0.394230963961 | gnomAD-4.0.0 | 2.56458E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78888E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8836 | likely_pathogenic | 0.9272 | pathogenic | -0.013 | Destabilizing | 0.916 | D | 0.593 | neutral | None | None | None | None | I |
| R/C | 0.343 | ambiguous | 0.4218 | ambiguous | -0.3 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | I |
| R/D | 0.9751 | likely_pathogenic | 0.9846 | pathogenic | -0.347 | Destabilizing | 0.996 | D | 0.594 | neutral | None | None | None | None | I |
| R/E | 0.8409 | likely_pathogenic | 0.8952 | pathogenic | -0.319 | Destabilizing | 0.985 | D | 0.561 | neutral | None | None | None | None | I |
| R/F | 0.7564 | likely_pathogenic | 0.827 | pathogenic | -0.37 | Destabilizing | 0.073 | N | 0.551 | neutral | None | None | None | None | I |
| R/G | 0.8381 | likely_pathogenic | 0.907 | pathogenic | -0.126 | Destabilizing | 0.944 | D | 0.558 | neutral | N | 0.494188706 | None | None | I |
| R/H | 0.2054 | likely_benign | 0.2264 | benign | -0.61 | Destabilizing | 0.996 | D | 0.536 | neutral | None | None | None | None | I |
| R/I | 0.4573 | ambiguous | 0.5694 | pathogenic | 0.235 | Stabilizing | 0.935 | D | 0.61 | neutral | N | 0.519898246 | None | None | I |
| R/K | 0.2241 | likely_benign | 0.2537 | benign | -0.24 | Destabilizing | 0.944 | D | 0.495 | neutral | N | 0.488708547 | None | None | I |
| R/L | 0.5139 | ambiguous | 0.6348 | pathogenic | 0.235 | Stabilizing | 0.845 | D | 0.593 | neutral | None | None | None | None | I |
| R/M | 0.6246 | likely_pathogenic | 0.728 | pathogenic | -0.143 | Destabilizing | 0.997 | D | 0.539 | neutral | None | None | None | None | I |
| R/N | 0.91 | likely_pathogenic | 0.9361 | pathogenic | -0.151 | Destabilizing | 0.996 | D | 0.544 | neutral | None | None | None | None | I |
| R/P | 0.978 | likely_pathogenic | 0.9893 | pathogenic | 0.169 | Stabilizing | 0.996 | D | 0.598 | neutral | None | None | None | None | I |
| R/Q | 0.2282 | likely_benign | 0.2828 | benign | -0.182 | Destabilizing | 0.996 | D | 0.553 | neutral | None | None | None | None | I |
| R/S | 0.8955 | likely_pathogenic | 0.9324 | pathogenic | -0.302 | Destabilizing | 0.983 | D | 0.549 | neutral | N | 0.50917982 | None | None | I |
| R/T | 0.7592 | likely_pathogenic | 0.834 | pathogenic | -0.182 | Destabilizing | 0.983 | D | 0.532 | neutral | D | 0.528939017 | None | None | I |
| R/V | 0.6434 | likely_pathogenic | 0.7348 | pathogenic | 0.169 | Stabilizing | 0.975 | D | 0.575 | neutral | None | None | None | None | I |
| R/W | 0.3179 | likely_benign | 0.4025 | ambiguous | -0.579 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | I |
| R/Y | 0.5477 | ambiguous | 0.6177 | pathogenic | -0.187 | Destabilizing | 0.95 | D | 0.589 | 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.