Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19633 | 59122;59123;59124 | chr2:178593311;178593310;178593309 | chr2:179458038;179458037;179458036 |
| N2AB | 17992 | 54199;54200;54201 | chr2:178593311;178593310;178593309 | chr2:179458038;179458037;179458036 |
| N2A | 17065 | 51418;51419;51420 | chr2:178593311;178593310;178593309 | chr2:179458038;179458037;179458036 |
| N2B | 10568 | 31927;31928;31929 | chr2:178593311;178593310;178593309 | chr2:179458038;179458037;179458036 |
| Novex-1 | 10693 | 32302;32303;32304 | chr2:178593311;178593310;178593309 | chr2:179458038;179458037;179458036 |
| Novex-2 | 10760 | 32503;32504;32505 | chr2:178593311;178593310;178593309 | chr2:179458038;179458037;179458036 |
| 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/L | None | None | 0.954 | N | 0.296 | 0.241 | 0.300784259202 | gnomAD-4.0.0 | 2.40065E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 3.66327E-05 |
| I/N | None | None | 0.989 | N | 0.575 | 0.47 | 0.784895281404 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | None | None | 0.925 | N | 0.508 | 0.298 | 0.522344865107 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8163 | likely_pathogenic | 0.7847 | pathogenic | -2.148 | Highly Destabilizing | 0.871 | D | 0.498 | neutral | None | None | None | None | I |
| I/C | 0.8909 | likely_pathogenic | 0.8826 | pathogenic | -1.167 | Destabilizing | 1.0 | D | 0.541 | neutral | None | None | None | None | I |
| I/D | 0.99 | likely_pathogenic | 0.9841 | pathogenic | -2.581 | Highly Destabilizing | 0.991 | D | 0.567 | neutral | None | None | None | None | I |
| I/E | 0.9723 | likely_pathogenic | 0.9595 | pathogenic | -2.298 | Highly Destabilizing | 0.991 | D | 0.537 | neutral | None | None | None | None | I |
| I/F | 0.556 | ambiguous | 0.4955 | ambiguous | -1.245 | Destabilizing | 0.998 | D | 0.487 | neutral | N | 0.46797497 | None | None | I |
| I/G | 0.9677 | likely_pathogenic | 0.9552 | pathogenic | -2.722 | Highly Destabilizing | 0.991 | D | 0.488 | neutral | None | None | None | None | I |
| I/H | 0.9669 | likely_pathogenic | 0.9521 | pathogenic | -2.364 | Highly Destabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | I |
| I/K | 0.9452 | likely_pathogenic | 0.9186 | pathogenic | -1.505 | Destabilizing | 0.991 | D | 0.547 | neutral | None | None | None | None | I |
| I/L | 0.1608 | likely_benign | 0.1435 | benign | -0.462 | Destabilizing | 0.954 | D | 0.296 | neutral | N | 0.42857166 | None | None | I |
| I/M | 0.2778 | likely_benign | 0.248 | benign | -0.397 | Destabilizing | 0.998 | D | 0.491 | neutral | N | 0.481964621 | None | None | I |
| I/N | 0.8953 | likely_pathogenic | 0.8512 | pathogenic | -2.016 | Highly Destabilizing | 0.989 | D | 0.575 | neutral | N | 0.512070117 | None | None | I |
| I/P | 0.9519 | likely_pathogenic | 0.937 | pathogenic | -1.008 | Destabilizing | 0.996 | D | 0.574 | neutral | None | None | None | None | I |
| I/Q | 0.9414 | likely_pathogenic | 0.9172 | pathogenic | -1.753 | Destabilizing | 0.996 | D | 0.583 | neutral | None | None | None | None | I |
| I/R | 0.9266 | likely_pathogenic | 0.8892 | pathogenic | -1.52 | Destabilizing | 0.996 | D | 0.569 | neutral | None | None | None | None | I |
| I/S | 0.8825 | likely_pathogenic | 0.8369 | pathogenic | -2.645 | Highly Destabilizing | 0.489 | N | 0.296 | neutral | N | 0.488019822 | None | None | I |
| I/T | 0.8299 | likely_pathogenic | 0.7861 | pathogenic | -2.204 | Highly Destabilizing | 0.925 | D | 0.508 | neutral | N | 0.475762601 | None | None | I |
| I/V | 0.1048 | likely_benign | 0.1067 | benign | -1.008 | Destabilizing | 0.954 | D | 0.313 | neutral | N | 0.464529674 | None | None | I |
| I/W | 0.9822 | likely_pathogenic | 0.9759 | pathogenic | -1.696 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
| I/Y | 0.9325 | likely_pathogenic | 0.9088 | pathogenic | -1.327 | Destabilizing | 0.999 | D | 0.525 | 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.