Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19862 | 59809;59810;59811 | chr2:178592421;178592420;178592419 | chr2:179457148;179457147;179457146 |
| N2AB | 18221 | 54886;54887;54888 | chr2:178592421;178592420;178592419 | chr2:179457148;179457147;179457146 |
| N2A | 17294 | 52105;52106;52107 | chr2:178592421;178592420;178592419 | chr2:179457148;179457147;179457146 |
| N2B | 10797 | 32614;32615;32616 | chr2:178592421;178592420;178592419 | chr2:179457148;179457147;179457146 |
| Novex-1 | 10922 | 32989;32990;32991 | chr2:178592421;178592420;178592419 | chr2:179457148;179457147;179457146 |
| Novex-2 | 10989 | 33190;33191;33192 | chr2:178592421;178592420;178592419 | chr2:179457148;179457147;179457146 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs16866406  |
0.094 | 0.008 | D | 0.387 | 0.19 | None | gnomAD-2.1.1 | 1.7341E-01 | None | None | None | None | I | None | 7.16591E-02 | 1.47846E-01 | None | 1.73353E-01 | 4.3298E-01 | None | 2.57761E-01 | None | 1.51472E-01 | 1.45017E-01 | 1.60569E-01 |
| P/L | rs16866406 |
0.094 | 0.008 | D | 0.387 | 0.19 | None | gnomAD-3.1.2 | 1.42446E-01 | None | None | None | None | I | None | 7.55679E-02 | 1.29443E-01 | 4.71366E-01 | 1.74352E-01 | 4.45762E-01 | None | 1.63206E-01 | 1.13924E-01 | 1.45726E-01 | 2.6495E-01 | 1.29187E-01 |
| P/L | rs16866406 |
0.094 | 0.008 | D | 0.387 | 0.19 | None | 1000 genomes | 2.13059E-01 | None | None | None | None | I | None | 6.66E-02 | 1.527E-01 | None | None | 4.573E-01 | 1.392E-01 | None | None | None | 2.781E-01 | None |
| P/L | rs16866406 |
0.094 | 0.008 | D | 0.387 | 0.19 | None | gnomAD-4.0.0 | 1.53377E-01 | None | None | None | None | I | None | 7.3695E-02 | 1.42795E-01 | None | 1.73981E-01 | 4.36539E-01 | None | 1.53056E-01 | 1.31692E-01 | 1.3915E-01 | 2.56485E-01 | 1.62679E-01 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0854 | likely_benign | 0.076 | benign | -0.277 | Destabilizing | 0.003 | N | 0.269 | neutral | N | 0.467506556 | None | None | I |
| P/C | 0.6074 | likely_pathogenic | 0.5007 | ambiguous | -0.662 | Destabilizing | 0.996 | D | 0.575 | neutral | None | None | None | None | I |
| P/D | 0.3935 | ambiguous | 0.3659 | ambiguous | -0.356 | Destabilizing | 0.961 | D | 0.381 | neutral | None | None | None | None | I |
| P/E | 0.2253 | likely_benign | 0.2171 | benign | -0.482 | Destabilizing | 0.923 | D | 0.355 | neutral | None | None | None | None | I |
| P/F | 0.6457 | likely_pathogenic | 0.5607 | ambiguous | -0.713 | Destabilizing | 0.858 | D | 0.55 | neutral | None | None | None | None | I |
| P/G | 0.3709 | ambiguous | 0.3345 | benign | -0.336 | Destabilizing | 0.633 | D | 0.393 | neutral | None | None | None | None | I |
| P/H | 0.2597 | likely_benign | 0.2216 | benign | -0.014 | Destabilizing | 0.996 | D | 0.525 | neutral | None | None | None | None | I |
| P/I | 0.3198 | likely_benign | 0.2487 | benign | -0.27 | Destabilizing | 0.858 | D | 0.469 | neutral | None | None | None | None | I |
| P/K | 0.2784 | likely_benign | 0.2468 | benign | -0.327 | Destabilizing | 0.923 | D | 0.354 | neutral | None | None | None | None | I |
| P/L | 0.148 | likely_benign | 0.1249 | benign | -0.27 | Destabilizing | 0.008 | N | 0.387 | neutral | D | 0.523687913 | None | None | I |
| P/M | 0.3204 | likely_benign | 0.2597 | benign | -0.463 | Destabilizing | 0.979 | D | 0.495 | neutral | None | None | None | None | I |
| P/N | 0.3509 | ambiguous | 0.292 | benign | -0.076 | Destabilizing | 0.961 | D | 0.486 | neutral | None | None | None | None | I |
| P/Q | 0.1833 | likely_benign | 0.1628 | benign | -0.307 | Destabilizing | 0.949 | D | 0.372 | neutral | D | 0.524957349 | None | None | I |
| P/R | 0.2167 | likely_benign | 0.1889 | benign | 0.121 | Stabilizing | 0.949 | D | 0.485 | neutral | N | 0.504312718 | None | None | I |
| P/S | 0.1522 | likely_benign | 0.1253 | benign | -0.361 | Destabilizing | 0.565 | D | 0.382 | neutral | N | 0.442472038 | None | None | I |
| P/T | 0.1146 | likely_benign | 0.0935 | benign | -0.396 | Destabilizing | 0.722 | D | 0.356 | neutral | N | 0.508526459 | None | None | I |
| P/V | 0.2101 | likely_benign | 0.1724 | benign | -0.243 | Destabilizing | 0.633 | D | 0.407 | neutral | None | None | None | None | I |
| P/W | 0.7705 | likely_pathogenic | 0.7187 | pathogenic | -0.787 | Destabilizing | 0.996 | D | 0.685 | prob.neutral | None | None | None | None | I |
| P/Y | 0.5879 | likely_pathogenic | 0.5082 | ambiguous | -0.492 | Destabilizing | 0.961 | D | 0.559 | 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.