Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3980 | 12163;12164;12165 | chr2:178741295;178741294;178741293 | chr2:179606022;179606021;179606020 |
| N2AB | 3663 | 11212;11213;11214 | chr2:178741295;178741294;178741293 | chr2:179606022;179606021;179606020 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3617 | 11074;11075;11076 | chr2:178741295;178741294;178741293 | chr2:179606022;179606021;179606020 |
| Novex-1 | 3742 | 11449;11450;11451 | chr2:178741295;178741294;178741293 | chr2:179606022;179606021;179606020 |
| Novex-2 | 3809 | 11650;11651;11652 | chr2:178741295;178741294;178741293 | chr2:179606022;179606021;179606020 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs372298992  |
0.015 | 0.473 | N | 0.303 | 0.278 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| T/I | rs372298992 |
0.015 | 0.473 | N | 0.303 | 0.278 | None | gnomAD-4.0.0 | 1.59116E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85793E-06 | 0 | 0 |
| T/S | rs1278282821 |
None | 0.01 | N | 0.137 | 0.109 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs1278282821 |
None | 0.01 | N | 0.137 | 0.109 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs1278282821 |
None | 0.01 | N | 0.137 | 0.109 | None | gnomAD-4.0.0 | 3.84282E-06 | None | None | None | None | I | None | 5.07168E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1075 | likely_benign | 0.1059 | benign | -0.33 | Destabilizing | 0.139 | N | 0.139 | neutral | N | 0.502160293 | None | None | I |
| T/C | 0.5734 | likely_pathogenic | 0.5324 | ambiguous | -0.251 | Destabilizing | 0.981 | D | 0.307 | neutral | None | None | None | None | I |
| T/D | 0.428 | ambiguous | 0.4442 | ambiguous | 0.265 | Stabilizing | 0.704 | D | 0.279 | neutral | None | None | None | None | I |
| T/E | 0.3522 | ambiguous | 0.3705 | ambiguous | 0.185 | Stabilizing | 0.704 | D | 0.281 | neutral | None | None | None | None | I |
| T/F | 0.4518 | ambiguous | 0.4184 | ambiguous | -0.902 | Destabilizing | 0.893 | D | 0.377 | neutral | None | None | None | None | I |
| T/G | 0.336 | likely_benign | 0.3307 | benign | -0.438 | Destabilizing | 0.329 | N | 0.298 | neutral | None | None | None | None | I |
| T/H | 0.3339 | likely_benign | 0.3302 | benign | -0.766 | Destabilizing | 0.981 | D | 0.324 | neutral | None | None | None | None | I |
| T/I | 0.3936 | ambiguous | 0.3549 | ambiguous | -0.169 | Destabilizing | 0.473 | N | 0.303 | neutral | N | 0.511072364 | None | None | I |
| T/K | 0.2694 | likely_benign | 0.2876 | benign | -0.267 | Destabilizing | 0.704 | D | 0.285 | neutral | None | None | None | None | I |
| T/L | 0.1771 | likely_benign | 0.1688 | benign | -0.169 | Destabilizing | 0.003 | N | 0.175 | neutral | None | None | None | None | I |
| T/M | 0.1582 | likely_benign | 0.1463 | benign | -0.006 | Destabilizing | 0.893 | D | 0.305 | neutral | None | None | None | None | I |
| T/N | 0.1608 | likely_benign | 0.1643 | benign | -0.07 | Destabilizing | 0.642 | D | 0.145 | neutral | N | 0.481512423 | None | None | I |
| T/P | 0.094 | likely_benign | 0.0854 | benign | -0.195 | Destabilizing | 0.002 | N | 0.157 | neutral | N | 0.443969642 | None | None | I |
| T/Q | 0.2819 | likely_benign | 0.2977 | benign | -0.286 | Destabilizing | 0.944 | D | 0.363 | neutral | None | None | None | None | I |
| T/R | 0.2026 | likely_benign | 0.2128 | benign | -0.044 | Destabilizing | 0.704 | D | 0.353 | neutral | None | None | None | None | I |
| T/S | 0.1391 | likely_benign | 0.1402 | benign | -0.277 | Destabilizing | 0.01 | N | 0.137 | neutral | N | 0.458384655 | None | None | I |
| T/V | 0.3064 | likely_benign | 0.277 | benign | -0.195 | Destabilizing | 0.329 | N | 0.188 | neutral | None | None | None | None | I |
| T/W | 0.793 | likely_pathogenic | 0.774 | pathogenic | -0.923 | Destabilizing | 0.995 | D | 0.336 | neutral | None | None | None | None | I |
| T/Y | 0.4452 | ambiguous | 0.4397 | ambiguous | -0.619 | Destabilizing | 0.944 | D | 0.343 | 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.