Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35906 | 107941;107942;107943 | chr2:178527272;178527271;178527270 | chr2:179391999;179391998;179391997 |
| N2AB | 34265 | 103018;103019;103020 | chr2:178527272;178527271;178527270 | chr2:179391999;179391998;179391997 |
| N2A | 33338 | 100237;100238;100239 | chr2:178527272;178527271;178527270 | chr2:179391999;179391998;179391997 |
| N2B | 26841 | 80746;80747;80748 | chr2:178527272;178527271;178527270 | chr2:179391999;179391998;179391997 |
| Novex-1 | 26966 | 81121;81122;81123 | chr2:178527272;178527271;178527270 | chr2:179391999;179391998;179391997 |
| Novex-2 | 27033 | 81322;81323;81324 | chr2:178527272;178527271;178527270 | chr2:179391999;179391998;179391997 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | None | None | 0.997 | N | 0.673 | 0.582 | 0.892327293303 | gnomAD-4.0.0 | 6.8735E-07 | None | None | None | -1.291(OBSL1) -0.74(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03377E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9317 | likely_pathogenic | 0.9214 | pathogenic | -2.268 | Highly Destabilizing | 0.91 | D | 0.61 | neutral | None | None | None | -1.689(OBSL1) -0.929(OBSCN) | N |
| I/C | 0.9701 | likely_pathogenic | 0.9613 | pathogenic | -1.477 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | -1.526(OBSL1) -0.613(OBSCN) | N |
| I/D | 0.9848 | likely_pathogenic | 0.9833 | pathogenic | -1.794 | Destabilizing | 0.998 | D | 0.674 | neutral | None | None | None | -1.358(OBSL1) -0.666(OBSCN) | N |
| I/E | 0.9717 | likely_pathogenic | 0.9689 | pathogenic | -1.71 | Destabilizing | 0.993 | D | 0.68 | prob.neutral | None | None | None | -1.251(OBSL1) -0.592(OBSCN) | N |
| I/F | 0.5229 | ambiguous | 0.4333 | ambiguous | -1.551 | Destabilizing | 0.991 | D | 0.55 | neutral | N | 0.496381206 | None | -0.211(OBSL1) -0.356(OBSCN) | N |
| I/G | 0.9875 | likely_pathogenic | 0.9859 | pathogenic | -2.694 | Highly Destabilizing | 0.993 | D | 0.678 | prob.neutral | None | None | None | -1.806(OBSL1) -0.992(OBSCN) | N |
| I/H | 0.956 | likely_pathogenic | 0.9434 | pathogenic | -1.899 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | -0.657(OBSL1) -0.408(OBSCN) | N |
| I/K | 0.9386 | likely_pathogenic | 0.9265 | pathogenic | -1.691 | Destabilizing | 0.993 | D | 0.675 | prob.neutral | None | None | None | -1.672(OBSL1) -1.02(OBSCN) | N |
| I/L | 0.3583 | ambiguous | 0.3094 | benign | -1.113 | Destabilizing | 0.58 | D | 0.301 | neutral | N | 0.478454268 | None | -1.325(OBSL1) -0.75(OBSCN) | N |
| I/M | 0.3578 | ambiguous | 0.3133 | benign | -0.854 | Destabilizing | 0.991 | D | 0.547 | neutral | N | 0.473261879 | None | -1.636(OBSL1) -0.866(OBSCN) | N |
| I/N | 0.8904 | likely_pathogenic | 0.8684 | pathogenic | -1.612 | Destabilizing | 0.997 | D | 0.673 | neutral | N | 0.494179161 | None | -1.291(OBSL1) -0.74(OBSCN) | N |
| I/P | 0.9917 | likely_pathogenic | 0.9914 | pathogenic | -1.471 | Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | -1.446(OBSL1) -0.807(OBSCN) | N |
| I/Q | 0.9489 | likely_pathogenic | 0.9395 | pathogenic | -1.685 | Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | -1.459(OBSL1) -0.737(OBSCN) | N |
| I/R | 0.9 | likely_pathogenic | 0.8792 | pathogenic | -1.14 | Destabilizing | 0.998 | D | 0.671 | neutral | None | None | None | -1.658(OBSL1) -1.232(OBSCN) | N |
| I/S | 0.907 | likely_pathogenic | 0.8944 | pathogenic | -2.314 | Highly Destabilizing | 0.991 | D | 0.649 | neutral | D | 0.525690855 | None | -1.711(OBSL1) -0.84(OBSCN) | N |
| I/T | 0.86 | likely_pathogenic | 0.839 | pathogenic | -2.092 | Highly Destabilizing | 0.939 | D | 0.629 | neutral | N | 0.47793698 | None | -1.633(OBSL1) -0.804(OBSCN) | N |
| I/V | 0.2343 | likely_benign | 0.2174 | benign | -1.471 | Destabilizing | 0.02 | N | 0.201 | neutral | N | 0.44920601 | None | -1.446(OBSL1) -0.807(OBSCN) | N |
| I/W | 0.9748 | likely_pathogenic | 0.967 | pathogenic | -1.694 | Destabilizing | 0.999 | D | 0.608 | neutral | None | None | None | -0.165(OBSL1) -0.611(OBSCN) | N |
| I/Y | 0.882 | likely_pathogenic | 0.842 | pathogenic | -1.484 | Destabilizing | 0.998 | D | 0.65 | neutral | None | None | None | -0.263(OBSL1) -0.505(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.