Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23977 | 72154;72155;72156 | chr2:178574203;178574202;178574201 | chr2:179438930;179438929;179438928 |
| N2AB | 22336 | 67231;67232;67233 | chr2:178574203;178574202;178574201 | chr2:179438930;179438929;179438928 |
| N2A | 21409 | 64450;64451;64452 | chr2:178574203;178574202;178574201 | chr2:179438930;179438929;179438928 |
| N2B | 14912 | 44959;44960;44961 | chr2:178574203;178574202;178574201 | chr2:179438930;179438929;179438928 |
| Novex-1 | 15037 | 45334;45335;45336 | chr2:178574203;178574202;178574201 | chr2:179438930;179438929;179438928 |
| Novex-2 | 15104 | 45535;45536;45537 | chr2:178574203;178574202;178574201 | chr2:179438930;179438929;179438928 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.472 | N | 0.224 | 0.243 | 0.215869574891 | gnomAD-4.0.0 | 9.60257E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.05E-05 | 0 | 0 |
| S/N | rs750632838  |
0.1 | 0.012 | N | 0.116 | 0.066 | 0.162503812791 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.12133E-04 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs750632838 |
0.1 | 0.012 | N | 0.116 | 0.066 | 0.162503812791 | gnomAD-4.0.0 | 7.96026E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11216E-04 | None | 0 | 0 | 2.85963E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1265 | likely_benign | 0.1374 | benign | -0.297 | Destabilizing | 0.373 | N | 0.277 | neutral | None | None | None | None | I |
| S/C | 0.1861 | likely_benign | 0.1915 | benign | -0.4 | Destabilizing | 0.994 | D | 0.334 | neutral | N | 0.486122586 | None | None | I |
| S/D | 0.7592 | likely_pathogenic | 0.7465 | pathogenic | 0.26 | Stabilizing | 0.59 | D | 0.225 | neutral | None | None | None | None | I |
| S/E | 0.8321 | likely_pathogenic | 0.819 | pathogenic | 0.17 | Stabilizing | 0.742 | D | 0.236 | neutral | None | None | None | None | I |
| S/F | 0.5572 | ambiguous | 0.5936 | pathogenic | -0.988 | Destabilizing | 0.953 | D | 0.4 | neutral | None | None | None | None | I |
| S/G | 0.1126 | likely_benign | 0.1086 | benign | -0.375 | Destabilizing | 0.472 | N | 0.224 | neutral | N | 0.458838639 | None | None | I |
| S/H | 0.6483 | likely_pathogenic | 0.6219 | pathogenic | -0.682 | Destabilizing | 0.953 | D | 0.317 | neutral | None | None | None | None | I |
| S/I | 0.3849 | ambiguous | 0.3821 | ambiguous | -0.224 | Destabilizing | 0.884 | D | 0.414 | neutral | N | 0.479445985 | None | None | I |
| S/K | 0.92 | likely_pathogenic | 0.9174 | pathogenic | -0.343 | Destabilizing | 0.742 | D | 0.238 | neutral | None | None | None | None | I |
| S/L | 0.2075 | likely_benign | 0.2332 | benign | -0.224 | Destabilizing | 0.59 | D | 0.34 | neutral | None | None | None | None | I |
| S/M | 0.3625 | ambiguous | 0.3695 | ambiguous | -0.241 | Destabilizing | 0.996 | D | 0.319 | neutral | None | None | None | None | I |
| S/N | 0.2663 | likely_benign | 0.2359 | benign | -0.146 | Destabilizing | 0.012 | N | 0.116 | neutral | N | 0.457742561 | None | None | I |
| S/P | 0.7308 | likely_pathogenic | 0.753 | pathogenic | -0.222 | Destabilizing | 0.953 | D | 0.346 | neutral | None | None | None | None | I |
| S/Q | 0.7342 | likely_pathogenic | 0.7127 | pathogenic | -0.33 | Destabilizing | 0.953 | D | 0.322 | neutral | None | None | None | None | I |
| S/R | 0.8639 | likely_pathogenic | 0.8681 | pathogenic | -0.111 | Destabilizing | 0.884 | D | 0.341 | neutral | N | 0.485582523 | None | None | I |
| S/T | 0.0964 | likely_benign | 0.0982 | benign | -0.248 | Destabilizing | 0.003 | N | 0.114 | neutral | N | 0.381551292 | None | None | I |
| S/V | 0.3617 | ambiguous | 0.3671 | ambiguous | -0.222 | Destabilizing | 0.59 | D | 0.4 | neutral | None | None | None | None | I |
| S/W | 0.673 | likely_pathogenic | 0.6983 | pathogenic | -1.048 | Destabilizing | 0.996 | D | 0.52 | neutral | None | None | None | None | I |
| S/Y | 0.4813 | ambiguous | 0.4944 | ambiguous | -0.731 | Destabilizing | 0.984 | D | 0.393 | 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.