Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21626 | 65101;65102;65103 | chr2:178584765;178584764;178584763 | chr2:179449492;179449491;179449490 |
| N2AB | 19985 | 60178;60179;60180 | chr2:178584765;178584764;178584763 | chr2:179449492;179449491;179449490 |
| N2A | 19058 | 57397;57398;57399 | chr2:178584765;178584764;178584763 | chr2:179449492;179449491;179449490 |
| N2B | 12561 | 37906;37907;37908 | chr2:178584765;178584764;178584763 | chr2:179449492;179449491;179449490 |
| Novex-1 | 12686 | 38281;38282;38283 | chr2:178584765;178584764;178584763 | chr2:179449492;179449491;179449490 |
| Novex-2 | 12753 | 38482;38483;38484 | chr2:178584765;178584764;178584763 | chr2:179449492;179449491;179449490 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.961 | N | 0.547 | 0.514 | 0.611689863146 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| P/T | rs2048562251  |
None | 0.248 | N | 0.262 | 0.327 | 0.335661160332 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| P/T | rs2048562251 |
None | 0.248 | N | 0.262 | 0.327 | 0.335661160332 | gnomAD-4.0.0 | 6.57739E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0835 | likely_benign | 0.0872 | benign | -0.887 | Destabilizing | 0.248 | N | 0.262 | neutral | N | 0.483793452 | None | None | N |
| P/C | 0.5228 | ambiguous | 0.5306 | ambiguous | -0.67 | Destabilizing | 0.351 | N | 0.433 | neutral | None | None | None | None | N |
| P/D | 0.6223 | likely_pathogenic | 0.6988 | pathogenic | -0.743 | Destabilizing | 0.996 | D | 0.413 | neutral | None | None | None | None | N |
| P/E | 0.3371 | likely_benign | 0.3941 | ambiguous | -0.841 | Destabilizing | 0.996 | D | 0.416 | neutral | None | None | None | None | N |
| P/F | 0.6601 | likely_pathogenic | 0.6963 | pathogenic | -0.978 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| P/G | 0.3784 | ambiguous | 0.3984 | ambiguous | -1.075 | Destabilizing | 0.97 | D | 0.468 | neutral | None | None | None | None | N |
| P/H | 0.2405 | likely_benign | 0.2937 | benign | -0.596 | Destabilizing | 1.0 | D | 0.535 | neutral | None | None | None | None | N |
| P/I | 0.387 | ambiguous | 0.4111 | ambiguous | -0.522 | Destabilizing | 0.991 | D | 0.596 | neutral | None | None | None | None | N |
| P/K | 0.2977 | likely_benign | 0.3624 | ambiguous | -0.764 | Destabilizing | 0.996 | D | 0.422 | neutral | None | None | None | None | N |
| P/L | 0.1611 | likely_benign | 0.1862 | benign | -0.522 | Destabilizing | 0.961 | D | 0.547 | neutral | N | 0.496977091 | None | None | N |
| P/M | 0.3899 | ambiguous | 0.415 | ambiguous | -0.372 | Destabilizing | 1.0 | D | 0.54 | neutral | None | None | None | None | N |
| P/N | 0.4587 | ambiguous | 0.5027 | ambiguous | -0.449 | Destabilizing | 0.996 | D | 0.519 | neutral | None | None | None | None | N |
| P/Q | 0.1821 | likely_benign | 0.212 | benign | -0.728 | Destabilizing | 0.998 | D | 0.43 | neutral | D | 0.530982031 | None | None | N |
| P/R | 0.1705 | likely_benign | 0.2275 | benign | -0.149 | Destabilizing | 0.994 | D | 0.529 | neutral | D | 0.532136824 | None | None | N |
| P/S | 0.1588 | likely_benign | 0.1752 | benign | -0.839 | Destabilizing | 0.925 | D | 0.401 | neutral | N | 0.486581837 | None | None | N |
| P/T | 0.1046 | likely_benign | 0.1127 | benign | -0.838 | Destabilizing | 0.248 | N | 0.262 | neutral | N | 0.507643812 | None | None | N |
| P/V | 0.2507 | likely_benign | 0.2692 | benign | -0.607 | Destabilizing | 0.97 | D | 0.466 | neutral | None | None | None | None | N |
| P/W | 0.7467 | likely_pathogenic | 0.8042 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| P/Y | 0.5719 | likely_pathogenic | 0.6229 | pathogenic | -0.777 | Destabilizing | 0.999 | D | 0.623 | 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.