Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17327 | 52204;52205;52206 | chr2:178609331;178609330;178609329 | chr2:179474058;179474057;179474056 |
| N2AB | 15686 | 47281;47282;47283 | chr2:178609331;178609330;178609329 | chr2:179474058;179474057;179474056 |
| N2A | 14759 | 44500;44501;44502 | chr2:178609331;178609330;178609329 | chr2:179474058;179474057;179474056 |
| N2B | 8262 | 25009;25010;25011 | chr2:178609331;178609330;178609329 | chr2:179474058;179474057;179474056 |
| Novex-1 | 8387 | 25384;25385;25386 | chr2:178609331;178609330;178609329 | chr2:179474058;179474057;179474056 |
| Novex-2 | 8454 | 25585;25586;25587 | chr2:178609331;178609330;178609329 | chr2:179474058;179474057;179474056 |
| 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/C | None | None | 0.997 | N | 0.417 | 0.411 | 0.433600339574 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/I | rs1447002596  |
-0.26 | 0.966 | D | 0.451 | 0.27 | 0.510407551169 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.01E-06 | 0 |
| S/I | rs1447002596 |
-0.26 | 0.966 | D | 0.451 | 0.27 | 0.510407551169 | gnomAD-4.0.0 | 1.37366E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80242E-06 | 0 | 0 |
| S/N | rs1447002596 |
None | 0.051 | N | 0.216 | 0.08 | 0.222439326576 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/N | rs1447002596 |
None | 0.051 | N | 0.216 | 0.08 | 0.222439326576 | gnomAD-4.0.0 | 1.24391E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69846E-06 | 0 | 0 |
| S/R | rs1244227970 |
None | 0.028 | N | 0.244 | 0.286 | 0.154104182512 | gnomAD-4.0.0 | 1.60947E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87848E-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 | 0.0881 | likely_benign | 0.0998 | benign | -0.195 | Destabilizing | 0.688 | D | 0.463 | neutral | None | None | None | None | N |
| S/C | 0.129 | likely_benign | 0.1443 | benign | -0.245 | Destabilizing | 0.997 | D | 0.417 | neutral | N | 0.489722162 | None | None | N |
| S/D | 0.2969 | likely_benign | 0.3396 | benign | -0.172 | Destabilizing | 0.728 | D | 0.4 | neutral | None | None | None | None | N |
| S/E | 0.3324 | likely_benign | 0.3883 | ambiguous | -0.288 | Destabilizing | 0.842 | D | 0.419 | neutral | None | None | None | None | N |
| S/F | 0.2474 | likely_benign | 0.282 | benign | -0.952 | Destabilizing | 0.974 | D | 0.431 | neutral | None | None | None | None | N |
| S/G | 0.0991 | likely_benign | 0.1128 | benign | -0.228 | Destabilizing | 0.625 | D | 0.437 | neutral | N | 0.493194434 | None | None | N |
| S/H | 0.2154 | likely_benign | 0.2451 | benign | -0.604 | Destabilizing | 0.037 | N | 0.364 | neutral | None | None | None | None | N |
| S/I | 0.2202 | likely_benign | 0.259 | benign | -0.236 | Destabilizing | 0.966 | D | 0.451 | neutral | D | 0.527037649 | None | None | N |
| S/K | 0.3361 | likely_benign | 0.3843 | ambiguous | -0.382 | Destabilizing | 0.728 | D | 0.423 | neutral | None | None | None | None | N |
| S/L | 0.1199 | likely_benign | 0.1422 | benign | -0.236 | Destabilizing | 0.842 | D | 0.397 | neutral | None | None | None | None | N |
| S/M | 0.2225 | likely_benign | 0.2504 | benign | -0.064 | Destabilizing | 0.998 | D | 0.402 | neutral | None | None | None | None | N |
| S/N | 0.1308 | likely_benign | 0.1609 | benign | -0.061 | Destabilizing | 0.051 | N | 0.216 | neutral | N | 0.491807567 | None | None | N |
| S/P | 0.6142 | likely_pathogenic | 0.6786 | pathogenic | -0.2 | Destabilizing | 0.991 | D | 0.399 | neutral | None | None | None | None | N |
| S/Q | 0.2883 | likely_benign | 0.3477 | ambiguous | -0.338 | Destabilizing | 0.949 | D | 0.406 | neutral | None | None | None | None | N |
| S/R | 0.2694 | likely_benign | 0.3294 | benign | -0.112 | Destabilizing | 0.028 | N | 0.244 | neutral | N | 0.473568523 | None | None | N |
| S/T | 0.0734 | likely_benign | 0.0767 | benign | -0.178 | Destabilizing | 0.801 | D | 0.458 | neutral | N | 0.450344947 | None | None | N |
| S/V | 0.2144 | likely_benign | 0.2531 | benign | -0.2 | Destabilizing | 0.974 | D | 0.39 | neutral | None | None | None | None | N |
| S/W | 0.3173 | likely_benign | 0.357 | ambiguous | -1.027 | Destabilizing | 0.998 | D | 0.576 | neutral | None | None | None | None | N |
| S/Y | 0.2044 | likely_benign | 0.2327 | benign | -0.719 | Destabilizing | 0.949 | D | 0.444 | 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.