Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1336 | 4231;4232;4233 | chr2:178779076;178779075;178779074 | chr2:179643803;179643802;179643801 |
| N2AB | 1336 | 4231;4232;4233 | chr2:178779076;178779075;178779074 | chr2:179643803;179643802;179643801 |
| N2A | 1336 | 4231;4232;4233 | chr2:178779076;178779075;178779074 | chr2:179643803;179643802;179643801 |
| N2B | 1290 | 4093;4094;4095 | chr2:178779076;178779075;178779074 | chr2:179643803;179643802;179643801 |
| Novex-1 | 1290 | 4093;4094;4095 | chr2:178779076;178779075;178779074 | chr2:179643803;179643802;179643801 |
| Novex-2 | 1290 | 4093;4094;4095 | chr2:178779076;178779075;178779074 | chr2:179643803;179643802;179643801 |
| Novex-3 | 1336 | 4231;4232;4233 | chr2:178779076;178779075;178779074 | chr2:179643803;179643802;179643801 |
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/S | rs1449428038  |
-0.685 | 0.896 | N | 0.465 | 0.34 | 0.250579442822 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| R/S | rs1449428038 |
-0.685 | 0.896 | N | 0.465 | 0.34 | 0.250579442822 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 | 0.8143 | likely_pathogenic | 0.7959 | pathogenic | -0.519 | Destabilizing | 0.919 | D | 0.467 | neutral | None | None | None | None | N |
| R/C | 0.5705 | likely_pathogenic | 0.5412 | ambiguous | -0.472 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| R/D | 0.8668 | likely_pathogenic | 0.8495 | pathogenic | -0.015 | Destabilizing | 0.976 | D | 0.484 | neutral | None | None | None | None | N |
| R/E | 0.7185 | likely_pathogenic | 0.704 | pathogenic | 0.145 | Stabilizing | 0.919 | D | 0.44 | neutral | None | None | None | None | N |
| R/F | 0.9071 | likely_pathogenic | 0.8938 | pathogenic | -0.22 | Destabilizing | 0.988 | D | 0.59 | neutral | None | None | None | None | N |
| R/G | 0.6812 | likely_pathogenic | 0.667 | pathogenic | -0.851 | Destabilizing | 0.896 | D | 0.443 | neutral | N | 0.480797006 | None | None | N |
| R/H | 0.2245 | likely_benign | 0.2145 | benign | -1.313 | Destabilizing | 0.034 | N | 0.159 | neutral | None | None | None | None | N |
| R/I | 0.6937 | likely_pathogenic | 0.6539 | pathogenic | 0.374 | Stabilizing | 0.984 | D | 0.583 | neutral | N | 0.493513599 | None | None | N |
| R/K | 0.244 | likely_benign | 0.2344 | benign | -0.359 | Destabilizing | 0.78 | D | 0.467 | neutral | N | 0.459408347 | None | None | N |
| R/L | 0.6134 | likely_pathogenic | 0.5862 | pathogenic | 0.374 | Stabilizing | 0.919 | D | 0.449 | neutral | None | None | None | None | N |
| R/M | 0.7782 | likely_pathogenic | 0.7494 | pathogenic | -0.197 | Destabilizing | 0.999 | D | 0.497 | neutral | None | None | None | None | N |
| R/N | 0.7686 | likely_pathogenic | 0.7359 | pathogenic | -0.15 | Destabilizing | 0.919 | D | 0.433 | neutral | None | None | None | None | N |
| R/P | 0.9056 | likely_pathogenic | 0.8835 | pathogenic | 0.098 | Stabilizing | 0.996 | D | 0.561 | neutral | None | None | None | None | N |
| R/Q | 0.2678 | likely_benign | 0.265 | benign | -0.138 | Destabilizing | 0.976 | D | 0.467 | neutral | None | None | None | None | N |
| R/S | 0.8549 | likely_pathogenic | 0.8351 | pathogenic | -0.747 | Destabilizing | 0.896 | D | 0.465 | neutral | N | 0.457572364 | None | None | N |
| R/T | 0.6844 | likely_pathogenic | 0.6418 | pathogenic | -0.387 | Destabilizing | 0.984 | D | 0.457 | neutral | N | 0.449432962 | None | None | N |
| R/V | 0.7723 | likely_pathogenic | 0.7498 | pathogenic | 0.098 | Stabilizing | 0.988 | D | 0.578 | neutral | None | None | None | None | N |
| R/W | 0.6328 | likely_pathogenic | 0.6056 | pathogenic | -0.002 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| R/Y | 0.7202 | likely_pathogenic | 0.6986 | pathogenic | 0.295 | Stabilizing | 0.976 | D | 0.546 | neutral | None | None | None | None | N |
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.