Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33614 | 101065;101066;101067 | chr2:178535775;178535774;178535773 | chr2:179400502;179400501;179400500 |
| N2AB | 31973 | 96142;96143;96144 | chr2:178535775;178535774;178535773 | chr2:179400502;179400501;179400500 |
| N2A | 31046 | 93361;93362;93363 | chr2:178535775;178535774;178535773 | chr2:179400502;179400501;179400500 |
| N2B | 24549 | 73870;73871;73872 | chr2:178535775;178535774;178535773 | chr2:179400502;179400501;179400500 |
| Novex-1 | 24674 | 74245;74246;74247 | chr2:178535775;178535774;178535773 | chr2:179400502;179400501;179400500 |
| Novex-2 | 24741 | 74446;74447;74448 | chr2:178535775;178535774;178535773 | chr2:179400502;179400501;179400500 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs879230745  |
None | 0.018 | N | 0.291 | 0.086 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/N | rs879230745 |
None | 0.018 | N | 0.291 | 0.086 | None | gnomAD-4.0.0 | 5.12999E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57474E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.185 | likely_benign | 0.1431 | benign | -0.288 | Destabilizing | 0.315 | N | 0.483 | neutral | None | None | None | None | N |
| S/C | 0.262 | likely_benign | 0.1641 | benign | -0.372 | Destabilizing | 0.999 | D | 0.568 | neutral | N | 0.50332763 | None | None | N |
| S/D | 0.8711 | likely_pathogenic | 0.7391 | pathogenic | 0.522 | Stabilizing | 0.883 | D | 0.516 | neutral | None | None | None | None | N |
| S/E | 0.9223 | likely_pathogenic | 0.7955 | pathogenic | 0.482 | Stabilizing | 0.955 | D | 0.516 | neutral | None | None | None | None | N |
| S/F | 0.7385 | likely_pathogenic | 0.5774 | pathogenic | -0.723 | Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | N |
| S/G | 0.2476 | likely_benign | 0.2109 | benign | -0.462 | Destabilizing | 0.897 | D | 0.535 | neutral | N | 0.484472511 | None | None | N |
| S/H | 0.7201 | likely_pathogenic | 0.5636 | ambiguous | -0.902 | Destabilizing | 0.998 | D | 0.575 | neutral | None | None | None | None | N |
| S/I | 0.5426 | ambiguous | 0.3923 | ambiguous | 0.045 | Stabilizing | 0.993 | D | 0.581 | neutral | N | 0.437121281 | None | None | N |
| S/K | 0.9797 | likely_pathogenic | 0.9274 | pathogenic | -0.29 | Destabilizing | 0.983 | D | 0.513 | neutral | None | None | None | None | N |
| S/L | 0.3943 | ambiguous | 0.2763 | benign | 0.045 | Stabilizing | 0.983 | D | 0.531 | neutral | None | None | None | None | N |
| S/M | 0.4495 | ambiguous | 0.3715 | ambiguous | -0.005 | Destabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | N |
| S/N | 0.2005 | likely_benign | 0.1801 | benign | -0.233 | Destabilizing | 0.018 | N | 0.291 | neutral | N | 0.391388991 | None | None | N |
| S/P | 0.9012 | likely_pathogenic | 0.8424 | pathogenic | -0.033 | Destabilizing | 0.997 | D | 0.572 | neutral | None | None | None | None | N |
| S/Q | 0.8475 | likely_pathogenic | 0.7228 | pathogenic | -0.337 | Destabilizing | 0.998 | D | 0.556 | neutral | None | None | None | None | N |
| S/R | 0.9659 | likely_pathogenic | 0.8769 | pathogenic | -0.225 | Destabilizing | 0.997 | D | 0.571 | neutral | N | 0.401392554 | None | None | N |
| S/T | 0.1375 | likely_benign | 0.1073 | benign | -0.29 | Destabilizing | 0.007 | N | 0.267 | neutral | N | 0.375531317 | None | None | N |
| S/V | 0.4953 | ambiguous | 0.3613 | ambiguous | -0.033 | Destabilizing | 0.955 | D | 0.532 | neutral | None | None | None | None | N |
| S/W | 0.8649 | likely_pathogenic | 0.7464 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.626 | neutral | None | None | None | None | N |
| S/Y | 0.6575 | likely_pathogenic | 0.4927 | ambiguous | -0.439 | Destabilizing | 0.999 | D | 0.593 | 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.