Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13825 | 41698;41699;41700 | chr2:178636098;178636097;178636096 | chr2:179500825;179500824;179500823 |
| N2AB | 12184 | 36775;36776;36777 | chr2:178636098;178636097;178636096 | chr2:179500825;179500824;179500823 |
| N2A | 11257 | 33994;33995;33996 | chr2:178636098;178636097;178636096 | chr2:179500825;179500824;179500823 |
| N2B | 4760 | 14503;14504;14505 | chr2:178636098;178636097;178636096 | chr2:179500825;179500824;179500823 |
| Novex-1 | 4885 | 14878;14879;14880 | chr2:178636098;178636097;178636096 | chr2:179500825;179500824;179500823 |
| Novex-2 | 4952 | 15079;15080;15081 | chr2:178636098;178636097;178636096 | chr2:179500825;179500824;179500823 |
| 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/G | None | None | 0.058 | N | 0.345 | 0.105 | 0.0884992946249 | gnomAD-4.0.0 | 4.10659E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39793E-06 | 0 | 0 |
| R/L | rs727504774  |
0.088 | 0.058 | N | 0.395 | 0.064 | 0.0884992946249 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 8.9E-06 | 0 |
| R/L | rs727504774 |
0.088 | 0.058 | N | 0.395 | 0.064 | 0.0884992946249 | gnomAD-4.0.0 | 6.84428E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99648E-07 | 0 | 0 |
| R/Q | rs727504774 |
-0.209 | 0.142 | N | 0.272 | 0.057 | 0.0611884634855 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 1.65399E-04 | 5.66E-05 | None | 0 | 5.18E-05 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs727504774 |
-0.209 | 0.142 | N | 0.272 | 0.057 | 0.0611884634855 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs727504774 |
-0.209 | 0.142 | N | 0.272 | 0.057 | 0.0611884634855 | gnomAD-4.0.0 | 2.60376E-05 | None | None | None | None | N | None | 9.35254E-05 | 3.33667E-05 | None | 0 | 2.23754E-05 | None | 0 | 1.64582E-04 | 2.54339E-05 | 0 | 1.60154E-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 | 0.4349 | ambiguous | 0.6044 | pathogenic | -0.816 | Destabilizing | 0.016 | N | 0.328 | neutral | None | None | None | None | N |
| R/C | 0.2422 | likely_benign | 0.2539 | benign | -0.715 | Destabilizing | 0.864 | D | 0.257 | neutral | None | None | None | None | N |
| R/D | 0.6896 | likely_pathogenic | 0.8328 | pathogenic | -0.165 | Destabilizing | 0.072 | N | 0.422 | neutral | None | None | None | None | N |
| R/E | 0.3426 | ambiguous | 0.5113 | ambiguous | -0.039 | Destabilizing | 0.016 | N | 0.256 | neutral | None | None | None | None | N |
| R/F | 0.5807 | likely_pathogenic | 0.7256 | pathogenic | -0.705 | Destabilizing | 0.356 | N | 0.391 | neutral | None | None | None | None | N |
| R/G | 0.3002 | likely_benign | 0.4713 | ambiguous | -1.133 | Destabilizing | 0.058 | N | 0.345 | neutral | N | 0.328273955 | None | None | N |
| R/H | 0.1137 | likely_benign | 0.1134 | benign | -1.536 | Destabilizing | None | N | 0.099 | neutral | None | None | None | None | N |
| R/I | 0.2651 | likely_benign | 0.3855 | ambiguous | 0.039 | Stabilizing | 0.356 | N | 0.45 | neutral | None | None | None | None | N |
| R/K | 0.0642 | likely_benign | 0.0732 | benign | -0.834 | Destabilizing | None | N | 0.079 | neutral | None | None | None | None | N |
| R/L | 0.2845 | likely_benign | 0.3691 | ambiguous | 0.039 | Stabilizing | 0.058 | N | 0.395 | neutral | N | 0.338407572 | None | None | N |
| R/M | 0.2553 | likely_benign | 0.3672 | ambiguous | -0.231 | Destabilizing | 0.628 | D | 0.277 | neutral | None | None | None | None | N |
| R/N | 0.4789 | ambiguous | 0.6418 | pathogenic | -0.311 | Destabilizing | 0.031 | N | 0.235 | neutral | None | None | None | None | N |
| R/P | 0.894 | likely_pathogenic | 0.9542 | pathogenic | -0.225 | Destabilizing | 0.232 | N | 0.401 | neutral | N | 0.361694012 | None | None | N |
| R/Q | 0.1159 | likely_benign | 0.1365 | benign | -0.467 | Destabilizing | 0.142 | N | 0.272 | neutral | N | 0.343671167 | None | None | N |
| R/S | 0.4899 | ambiguous | 0.6597 | pathogenic | -1.053 | Destabilizing | 0.016 | N | 0.363 | neutral | None | None | None | None | N |
| R/T | 0.2705 | likely_benign | 0.3854 | ambiguous | -0.74 | Destabilizing | 0.072 | N | 0.389 | neutral | None | None | None | None | N |
| R/V | 0.3476 | ambiguous | 0.4757 | ambiguous | -0.225 | Destabilizing | 0.072 | N | 0.432 | neutral | None | None | None | None | N |
| R/W | 0.2598 | likely_benign | 0.3584 | ambiguous | -0.384 | Destabilizing | 0.864 | D | 0.285 | neutral | None | None | None | None | N |
| R/Y | 0.4301 | ambiguous | 0.5661 | pathogenic | -0.074 | Destabilizing | 0.12 | N | 0.433 | 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.