Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35933 | 108022;108023;108024 | chr2:178527191;178527190;178527189 | chr2:179391918;179391917;179391916 |
| N2AB | 34292 | 103099;103100;103101 | chr2:178527191;178527190;178527189 | chr2:179391918;179391917;179391916 |
| N2A | 33365 | 100318;100319;100320 | chr2:178527191;178527190;178527189 | chr2:179391918;179391917;179391916 |
| N2B | 26868 | 80827;80828;80829 | chr2:178527191;178527190;178527189 | chr2:179391918;179391917;179391916 |
| Novex-1 | 26993 | 81202;81203;81204 | chr2:178527191;178527190;178527189 | chr2:179391918;179391917;179391916 |
| Novex-2 | 27060 | 81403;81404;81405 | chr2:178527191;178527190;178527189 | chr2:179391918;179391917;179391916 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs1686762598  |
None | 0.497 | N | 0.407 | 0.172 | 0.0762999501168 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | 0.897(OBSL1) 0.058(OBSCN) | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs1686762598 |
None | 0.497 | N | 0.407 | 0.172 | 0.0762999501168 | gnomAD-4.0.0 | 5.12338E-06 | None | None | None | 0.897(OBSL1) 0.058(OBSCN) | N | None | 3.38238E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.7849E-06 | 0 | 0 |
| G/R | rs1575170417 |
None | 0.002 | N | 0.394 | 0.067 | 0.225902525712 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | 0.188(OBSL1) -0.494(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1323 | likely_benign | 0.1373 | benign | -0.149 | Destabilizing | 0.001 | N | 0.287 | neutral | N | 0.473564871 | None | 0.213(OBSL1) -0.32(OBSCN) | N |
| G/C | 0.2115 | likely_benign | 0.2345 | benign | -0.865 | Destabilizing | 0.883 | D | 0.668 | neutral | N | 0.479965342 | None | 0.99(OBSL1) 0.489(OBSCN) | N |
| G/D | 0.1875 | likely_benign | 0.1874 | benign | -0.288 | Destabilizing | 0.497 | N | 0.407 | neutral | N | 0.411625404 | None | 0.897(OBSL1) 0.058(OBSCN) | N |
| G/E | 0.1855 | likely_benign | 0.1757 | benign | -0.444 | Destabilizing | 0.567 | D | 0.498 | neutral | None | None | None | 0.865(OBSL1) 0.006(OBSCN) | N |
| G/F | 0.6145 | likely_pathogenic | 0.6346 | pathogenic | -0.919 | Destabilizing | 0.726 | D | 0.65 | neutral | None | None | None | 1.096(OBSL1) 0.621(OBSCN) | N |
| G/H | 0.2404 | likely_benign | 0.2541 | benign | -0.308 | Destabilizing | 0.909 | D | 0.599 | neutral | None | None | None | 1.139(OBSL1) 0.401(OBSCN) | N |
| G/I | 0.483 | ambiguous | 0.4855 | ambiguous | -0.399 | Destabilizing | 0.567 | D | 0.659 | neutral | None | None | None | 0.42(OBSL1) -0.166(OBSCN) | N |
| G/K | 0.2415 | likely_benign | 0.1946 | benign | -0.468 | Destabilizing | 0.157 | N | 0.516 | neutral | None | None | None | 0.655(OBSL1) -0.036(OBSCN) | N |
| G/L | 0.4477 | ambiguous | 0.4588 | ambiguous | -0.399 | Destabilizing | 0.396 | N | 0.586 | neutral | None | None | None | 0.42(OBSL1) -0.166(OBSCN) | N |
| G/M | 0.5051 | ambiguous | 0.5111 | ambiguous | -0.517 | Destabilizing | 0.909 | D | 0.646 | neutral | None | None | None | 0.838(OBSL1) 0.248(OBSCN) | N |
| G/N | 0.2228 | likely_benign | 0.2328 | benign | -0.197 | Destabilizing | 0.567 | D | 0.353 | neutral | None | None | None | 0.514(OBSL1) 0.047(OBSCN) | N |
| G/P | 0.8374 | likely_pathogenic | 0.8568 | pathogenic | -0.29 | Destabilizing | 0.567 | D | 0.587 | neutral | None | None | None | 0.358(OBSL1) -0.211(OBSCN) | N |
| G/Q | 0.1713 | likely_benign | 0.1618 | benign | -0.436 | Destabilizing | 0.567 | D | 0.588 | neutral | None | None | None | 0.709(OBSL1) 0.175(OBSCN) | N |
| G/R | 0.1224 | likely_benign | 0.1005 | benign | -0.131 | Destabilizing | 0.002 | N | 0.394 | neutral | N | 0.46646554 | None | 0.188(OBSL1) -0.494(OBSCN) | N |
| G/S | 0.1006 | likely_benign | 0.1091 | benign | -0.359 | Destabilizing | 0.004 | N | 0.281 | neutral | N | 0.418538307 | None | 0.538(OBSL1) 0.17(OBSCN) | N |
| G/T | 0.2678 | likely_benign | 0.2765 | benign | -0.444 | Destabilizing | 0.157 | N | 0.517 | neutral | None | None | None | 0.566(OBSL1) 0.172(OBSCN) | N |
| G/V | 0.3588 | ambiguous | 0.3697 | ambiguous | -0.29 | Destabilizing | 0.331 | N | 0.637 | neutral | N | 0.4939215 | None | 0.358(OBSL1) -0.211(OBSCN) | N |
| G/W | 0.418 | ambiguous | 0.4077 | ambiguous | -1.035 | Destabilizing | 0.968 | D | 0.655 | neutral | None | None | None | 1.137(OBSL1) 0.692(OBSCN) | N |
| G/Y | 0.4386 | ambiguous | 0.4482 | ambiguous | -0.704 | Destabilizing | 0.726 | D | 0.651 | neutral | None | None | None | 1.143(OBSL1) 0.682(OBSCN) | 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.