Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8403 | 25432;25433;25434 | chr2:178717667;178717666;178717665 | chr2:179582394;179582393;179582392 |
| N2AB | 8086 | 24481;24482;24483 | chr2:178717667;178717666;178717665 | chr2:179582394;179582393;179582392 |
| N2A | 7159 | 21700;21701;21702 | chr2:178717667;178717666;178717665 | chr2:179582394;179582393;179582392 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs758110981  |
0.358 | 0.001 | N | 0.173 | 0.145 | 0.0611884634855 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/G | rs758110981 |
0.358 | 0.001 | N | 0.173 | 0.145 | 0.0611884634855 | gnomAD-4.0.0 | 2.73746E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59841E-06 | 0 | 0 |
| D/V | None | None | 0.283 | N | 0.348 | 0.174 | 0.326074293725 | gnomAD-4.0.0 | 6.84364E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99603E-07 | 0 | 0 |
| D/Y | rs779553584 |
0.119 | 0.99 | N | 0.29 | 0.248 | 0.38242337071 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 0 | 0 |
| D/Y | rs779553584 |
0.119 | 0.99 | N | 0.29 | 0.248 | 0.38242337071 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs779553584 |
0.119 | 0.99 | N | 0.29 | 0.248 | 0.38242337071 | gnomAD-4.0.0 | 5.12681E-06 | None | None | None | None | I | None | 3.38318E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.6824E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2377 | likely_benign | 0.2165 | benign | -0.142 | Destabilizing | 0.206 | N | 0.335 | neutral | N | 0.495198431 | None | None | I |
| D/C | 0.7411 | likely_pathogenic | 0.7152 | pathogenic | 0.199 | Stabilizing | 0.975 | D | 0.292 | neutral | None | None | None | None | I |
| D/E | 0.285 | likely_benign | 0.2525 | benign | -0.208 | Destabilizing | None | N | 0.257 | neutral | N | 0.504183274 | None | None | I |
| D/F | 0.7206 | likely_pathogenic | 0.7133 | pathogenic | -0.295 | Destabilizing | 0.977 | D | 0.293 | neutral | None | None | None | None | I |
| D/G | 0.1809 | likely_benign | 0.1664 | benign | -0.303 | Destabilizing | 0.001 | N | 0.173 | neutral | N | 0.444825539 | None | None | I |
| D/H | 0.3341 | likely_benign | 0.3331 | benign | -0.131 | Destabilizing | 0.923 | D | 0.296 | neutral | N | 0.449133704 | None | None | I |
| D/I | 0.5729 | likely_pathogenic | 0.5488 | ambiguous | 0.221 | Stabilizing | 0.954 | D | 0.321 | neutral | None | None | None | None | I |
| D/K | 0.5217 | ambiguous | 0.4948 | ambiguous | 0.372 | Stabilizing | 0.749 | D | 0.327 | neutral | None | None | None | None | I |
| D/L | 0.5656 | likely_pathogenic | 0.5449 | ambiguous | 0.221 | Stabilizing | 0.749 | D | 0.344 | neutral | None | None | None | None | I |
| D/M | 0.7334 | likely_pathogenic | 0.715 | pathogenic | 0.363 | Stabilizing | 0.995 | D | 0.289 | neutral | None | None | None | None | I |
| D/N | 0.1019 | likely_benign | 0.0986 | benign | 0.267 | Stabilizing | 0.359 | N | 0.275 | neutral | N | 0.470724061 | None | None | I |
| D/P | 0.8673 | likely_pathogenic | 0.8603 | pathogenic | 0.121 | Stabilizing | 0.456 | N | 0.327 | neutral | None | None | None | None | I |
| D/Q | 0.4913 | ambiguous | 0.4602 | ambiguous | 0.268 | Stabilizing | 0.796 | D | 0.278 | neutral | None | None | None | None | I |
| D/R | 0.5131 | ambiguous | 0.4975 | ambiguous | 0.466 | Stabilizing | 0.954 | D | 0.347 | neutral | None | None | None | None | I |
| D/S | 0.1213 | likely_benign | 0.1155 | benign | 0.135 | Stabilizing | 0.061 | N | 0.23 | neutral | None | None | None | None | I |
| D/T | 0.2468 | likely_benign | 0.2363 | benign | 0.25 | Stabilizing | 0.01 | N | 0.293 | neutral | None | None | None | None | I |
| D/V | 0.3643 | ambiguous | 0.3457 | ambiguous | 0.121 | Stabilizing | 0.283 | N | 0.348 | neutral | N | 0.451615693 | None | None | I |
| D/W | 0.9383 | likely_pathogenic | 0.9364 | pathogenic | -0.252 | Destabilizing | 0.998 | D | 0.366 | neutral | None | None | None | None | I |
| D/Y | 0.3658 | ambiguous | 0.3531 | ambiguous | -0.08 | Destabilizing | 0.99 | D | 0.29 | neutral | N | 0.459351147 | 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.