Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35937 | 108034;108035;108036 | chr2:178527179;178527178;178527177 | chr2:179391906;179391905;179391904 |
| N2AB | 34296 | 103111;103112;103113 | chr2:178527179;178527178;178527177 | chr2:179391906;179391905;179391904 |
| N2A | 33369 | 100330;100331;100332 | chr2:178527179;178527178;178527177 | chr2:179391906;179391905;179391904 |
| N2B | 26872 | 80839;80840;80841 | chr2:178527179;178527178;178527177 | chr2:179391906;179391905;179391904 |
| Novex-1 | 26997 | 81214;81215;81216 | chr2:178527179;178527178;178527177 | chr2:179391906;179391905;179391904 |
| Novex-2 | 27064 | 81415;81416;81417 | chr2:178527179;178527178;178527177 | chr2:179391906;179391905;179391904 |
| 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 | 0.989 | N | 0.705 | 0.639 | 0.8904792502 | gnomAD-4.0.0 | 6.84143E-07 | None | None | None | -0.703(OBSL1) -0.708(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15939E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8414 | likely_pathogenic | 0.852 | pathogenic | -2.436 | Highly Destabilizing | 0.525 | D | 0.548 | neutral | None | None | None | -0.732(OBSL1) -0.439(OBSCN) | N |
| I/C | 0.905 | likely_pathogenic | 0.9101 | pathogenic | -1.572 | Destabilizing | 0.998 | D | 0.597 | neutral | None | None | None | -1.12(OBSL1) -0.802(OBSCN) | N |
| I/D | 0.9574 | likely_pathogenic | 0.9577 | pathogenic | -2.419 | Highly Destabilizing | 0.991 | D | 0.691 | prob.neutral | None | None | None | -0.704(OBSL1) -0.647(OBSCN) | N |
| I/E | 0.9099 | likely_pathogenic | 0.9143 | pathogenic | -2.197 | Highly Destabilizing | 0.974 | D | 0.672 | neutral | None | None | None | -0.772(OBSL1) -0.804(OBSCN) | N |
| I/F | 0.2552 | likely_benign | 0.2578 | benign | -1.456 | Destabilizing | 0.012 | N | 0.376 | neutral | D | 0.536121279 | None | -1.406(OBSL1) -0.364(OBSCN) | N |
| I/G | 0.9337 | likely_pathogenic | 0.937 | pathogenic | -2.98 | Highly Destabilizing | 0.974 | D | 0.662 | neutral | None | None | None | -0.676(OBSL1) -0.353(OBSCN) | N |
| I/H | 0.8484 | likely_pathogenic | 0.8415 | pathogenic | -2.371 | Highly Destabilizing | 0.998 | D | 0.664 | neutral | None | None | None | -1.314(OBSL1) 0.005(OBSCN) | N |
| I/K | 0.8049 | likely_pathogenic | 0.8031 | pathogenic | -1.728 | Destabilizing | 0.974 | D | 0.674 | neutral | None | None | None | -1.069(OBSL1) -1.077(OBSCN) | N |
| I/L | 0.1454 | likely_benign | 0.1448 | benign | -0.864 | Destabilizing | 0.267 | N | 0.399 | neutral | N | 0.451899598 | None | -0.939(OBSL1) -0.748(OBSCN) | N |
| I/M | 0.1629 | likely_benign | 0.1659 | benign | -0.735 | Destabilizing | 0.966 | D | 0.62 | neutral | N | 0.492826489 | None | -1.288(OBSL1) -0.724(OBSCN) | N |
| I/N | 0.6778 | likely_pathogenic | 0.6704 | pathogenic | -1.973 | Destabilizing | 0.989 | D | 0.705 | prob.neutral | N | 0.521414903 | None | -0.703(OBSL1) -0.708(OBSCN) | N |
| I/P | 0.9314 | likely_pathogenic | 0.9342 | pathogenic | -1.369 | Destabilizing | 0.991 | D | 0.705 | prob.neutral | None | None | None | -0.865(OBSL1) -0.638(OBSCN) | N |
| I/Q | 0.8199 | likely_pathogenic | 0.8174 | pathogenic | -1.84 | Destabilizing | 0.991 | D | 0.691 | prob.neutral | None | None | None | -0.761(OBSL1) -0.753(OBSCN) | N |
| I/R | 0.7379 | likely_pathogenic | 0.7347 | pathogenic | -1.513 | Destabilizing | 0.991 | D | 0.695 | prob.neutral | None | None | None | -1.118(OBSL1) -1.087(OBSCN) | N |
| I/S | 0.8036 | likely_pathogenic | 0.8046 | pathogenic | -2.709 | Highly Destabilizing | 0.966 | D | 0.606 | neutral | N | 0.514324558 | None | -0.649(OBSL1) -0.415(OBSCN) | N |
| I/T | 0.8073 | likely_pathogenic | 0.82 | pathogenic | -2.33 | Highly Destabilizing | 0.801 | D | 0.559 | neutral | D | 0.529475844 | None | -0.73(OBSL1) -0.567(OBSCN) | N |
| I/V | 0.1967 | likely_benign | 0.2102 | benign | -1.369 | Destabilizing | 0.005 | N | 0.163 | neutral | N | 0.505507583 | None | -0.865(OBSL1) -0.638(OBSCN) | N |
| I/W | 0.8679 | likely_pathogenic | 0.8661 | pathogenic | -1.78 | Destabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | -1.799(OBSL1) -0.52(OBSCN) | N |
| I/Y | 0.6793 | likely_pathogenic | 0.669 | pathogenic | -1.495 | Destabilizing | 0.904 | D | 0.616 | neutral | None | None | None | -1.461(OBSL1) -0.41(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.