Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17864 | 53815;53816;53817 | chr2:178605705;178605704;178605703 | chr2:179470432;179470431;179470430 |
| N2AB | 16223 | 48892;48893;48894 | chr2:178605705;178605704;178605703 | chr2:179470432;179470431;179470430 |
| N2A | 15296 | 46111;46112;46113 | chr2:178605705;178605704;178605703 | chr2:179470432;179470431;179470430 |
| N2B | 8799 | 26620;26621;26622 | chr2:178605705;178605704;178605703 | chr2:179470432;179470431;179470430 |
| Novex-1 | 8924 | 26995;26996;26997 | chr2:178605705;178605704;178605703 | chr2:179470432;179470431;179470430 |
| Novex-2 | 8991 | 27196;27197;27198 | chr2:178605705;178605704;178605703 | chr2:179470432;179470431;179470430 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs375309278  |
-0.626 | 0.454 | N | 0.392 | 0.072 | None | gnomAD-2.1.1 | 4.27E-05 | None | None | None | None | N | None | 4.31406E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs375309278 |
-0.626 | 0.454 | N | 0.392 | 0.072 | None | gnomAD-3.1.2 | 1.11824E-04 | None | None | None | None | N | None | 3.61987E-04 | 6.56E-05 | 0 | 0 | 1.94477E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs375309278 |
-0.626 | 0.454 | N | 0.392 | 0.072 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/A | rs375309278 |
-0.626 | 0.454 | N | 0.392 | 0.072 | None | gnomAD-4.0.0 | 1.96307E-05 | None | None | None | None | N | None | 3.03281E-04 | 1.98981E-05 | None | 0 | 2.30638E-05 | None | 0 | 0 | 5.28726E-06 | 0 | 0 |
| T/K | rs373176585 |
None | 0.801 | N | 0.423 | 0.242 | 0.366085729538 | gnomAD-4.0.0 | 7.25273E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.42759E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1271 | likely_benign | 0.1007 | benign | -0.712 | Destabilizing | 0.454 | N | 0.392 | neutral | N | 0.471607575 | None | None | N |
| T/C | 0.5874 | likely_pathogenic | 0.4867 | ambiguous | -0.672 | Destabilizing | 0.998 | D | 0.466 | neutral | None | None | None | None | N |
| T/D | 0.6843 | likely_pathogenic | 0.594 | pathogenic | -1.28 | Destabilizing | 0.842 | D | 0.423 | neutral | None | None | None | None | N |
| T/E | 0.7123 | likely_pathogenic | 0.6061 | pathogenic | -1.269 | Destabilizing | 0.842 | D | 0.427 | neutral | None | None | None | None | N |
| T/F | 0.5972 | likely_pathogenic | 0.4764 | ambiguous | -0.974 | Destabilizing | 0.991 | D | 0.536 | neutral | None | None | None | None | N |
| T/G | 0.2083 | likely_benign | 0.1665 | benign | -0.951 | Destabilizing | 0.007 | N | 0.269 | neutral | None | None | None | None | N |
| T/H | 0.5787 | likely_pathogenic | 0.4954 | ambiguous | -1.357 | Destabilizing | 0.998 | D | 0.503 | neutral | None | None | None | None | N |
| T/I | 0.5811 | likely_pathogenic | 0.4416 | ambiguous | -0.164 | Destabilizing | 0.966 | D | 0.472 | neutral | N | 0.502181198 | None | None | N |
| T/K | 0.6887 | likely_pathogenic | 0.5843 | pathogenic | -0.738 | Destabilizing | 0.801 | D | 0.423 | neutral | N | 0.482902004 | None | None | N |
| T/L | 0.2267 | likely_benign | 0.1902 | benign | -0.164 | Destabilizing | 0.915 | D | 0.395 | neutral | None | None | None | None | N |
| T/M | 0.2015 | likely_benign | 0.1729 | benign | 0.242 | Stabilizing | 0.998 | D | 0.463 | neutral | None | None | None | None | N |
| T/N | 0.2462 | likely_benign | 0.2206 | benign | -0.916 | Destabilizing | 0.842 | D | 0.406 | neutral | None | None | None | None | N |
| T/P | 0.5587 | ambiguous | 0.4269 | ambiguous | -0.316 | Destabilizing | 0.966 | D | 0.453 | neutral | N | 0.501314406 | None | None | N |
| T/Q | 0.5192 | ambiguous | 0.4311 | ambiguous | -1.191 | Destabilizing | 0.974 | D | 0.477 | neutral | None | None | None | None | N |
| T/R | 0.6595 | likely_pathogenic | 0.5548 | ambiguous | -0.459 | Destabilizing | 0.966 | D | 0.472 | neutral | N | 0.501661123 | None | None | N |
| T/S | 0.1204 | likely_benign | 0.108 | benign | -1.023 | Destabilizing | 0.062 | N | 0.111 | neutral | N | 0.385543241 | None | None | N |
| T/V | 0.368 | ambiguous | 0.2617 | benign | -0.316 | Destabilizing | 0.915 | D | 0.376 | neutral | None | None | None | None | N |
| T/W | 0.9043 | likely_pathogenic | 0.8497 | pathogenic | -0.978 | Destabilizing | 0.998 | D | 0.584 | neutral | None | None | None | None | N |
| T/Y | 0.6647 | likely_pathogenic | 0.5695 | pathogenic | -0.654 | Destabilizing | 0.991 | D | 0.532 | 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.