Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21187 | 63784;63785;63786 | chr2:178587750;178587749;178587748 | chr2:179452477;179452476;179452475 |
| N2AB | 19546 | 58861;58862;58863 | chr2:178587750;178587749;178587748 | chr2:179452477;179452476;179452475 |
| N2A | 18619 | 56080;56081;56082 | chr2:178587750;178587749;178587748 | chr2:179452477;179452476;179452475 |
| N2B | 12122 | 36589;36590;36591 | chr2:178587750;178587749;178587748 | chr2:179452477;179452476;179452475 |
| Novex-1 | 12247 | 36964;36965;36966 | chr2:178587750;178587749;178587748 | chr2:179452477;179452476;179452475 |
| Novex-2 | 12314 | 37165;37166;37167 | chr2:178587750;178587749;178587748 | chr2:179452477;179452476;179452475 |
| 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 | rs368288863  |
-0.173 | 0.892 | N | 0.575 | 0.467 | None | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs368288863 |
-0.173 | 0.892 | N | 0.575 | 0.467 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/G | rs368288863 |
-0.173 | 0.892 | N | 0.575 | 0.467 | None | gnomAD-4.0.0 | 2.48153E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39306E-06 | 0 | 0 |
| R/K | None | None | 0.63 | N | 0.537 | 0.213 | 0.326616659874 | gnomAD-4.0.0 | 2.73989E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60065E-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 | 0.9544 | likely_pathogenic | 0.9455 | pathogenic | 0.08 | Stabilizing | 0.916 | D | 0.603 | neutral | None | None | None | None | I |
| R/C | 0.6973 | likely_pathogenic | 0.6762 | pathogenic | -0.127 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | I |
| R/D | 0.9824 | likely_pathogenic | 0.9791 | pathogenic | -0.113 | Destabilizing | 0.845 | D | 0.583 | neutral | None | None | None | None | I |
| R/E | 0.8952 | likely_pathogenic | 0.8749 | pathogenic | -0.038 | Destabilizing | 0.033 | N | 0.399 | neutral | None | None | None | None | I |
| R/F | 0.9707 | likely_pathogenic | 0.9654 | pathogenic | -0.104 | Destabilizing | 0.996 | D | 0.663 | neutral | None | None | None | None | I |
| R/G | 0.9228 | likely_pathogenic | 0.9076 | pathogenic | -0.125 | Destabilizing | 0.892 | D | 0.575 | neutral | N | 0.520041642 | None | None | I |
| R/H | 0.3512 | ambiguous | 0.3238 | benign | -0.669 | Destabilizing | 0.987 | D | 0.591 | neutral | None | None | None | None | I |
| R/I | 0.939 | likely_pathogenic | 0.9235 | pathogenic | 0.588 | Stabilizing | 0.983 | D | 0.664 | neutral | N | 0.502190877 | None | None | I |
| R/K | 0.289 | likely_benign | 0.2628 | benign | -0.025 | Destabilizing | 0.63 | D | 0.537 | neutral | N | 0.474875245 | None | None | I |
| R/L | 0.8445 | likely_pathogenic | 0.8138 | pathogenic | 0.588 | Stabilizing | 0.975 | D | 0.569 | neutral | None | None | None | None | I |
| R/M | 0.9025 | likely_pathogenic | 0.8727 | pathogenic | 0.056 | Stabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | I |
| R/N | 0.9643 | likely_pathogenic | 0.957 | pathogenic | 0.119 | Stabilizing | 0.975 | D | 0.577 | neutral | None | None | None | None | I |
| R/P | 0.898 | likely_pathogenic | 0.8828 | pathogenic | 0.44 | Stabilizing | 0.987 | D | 0.649 | neutral | None | None | None | None | I |
| R/Q | 0.3711 | ambiguous | 0.3353 | benign | 0.075 | Stabilizing | 0.845 | D | 0.586 | neutral | None | None | None | None | I |
| R/S | 0.9682 | likely_pathogenic | 0.9624 | pathogenic | -0.166 | Destabilizing | 0.892 | D | 0.599 | neutral | N | 0.491387095 | None | None | I |
| R/T | 0.9266 | likely_pathogenic | 0.9026 | pathogenic | 0.048 | Stabilizing | 0.967 | D | 0.571 | neutral | N | 0.498290083 | None | None | I |
| R/V | 0.9415 | likely_pathogenic | 0.9295 | pathogenic | 0.44 | Stabilizing | 0.987 | D | 0.663 | neutral | None | None | None | None | I |
| R/W | 0.7203 | likely_pathogenic | 0.685 | pathogenic | -0.192 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | I |
| R/Y | 0.9079 | likely_pathogenic | 0.8998 | pathogenic | 0.224 | Stabilizing | 0.996 | D | 0.645 | 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.