Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4747 | 14464;14465;14466 | chr2:178738214;178738213;178738212 | chr2:179602941;179602940;179602939 |
| N2AB | 4430 | 13513;13514;13515 | chr2:178738214;178738213;178738212 | chr2:179602941;179602940;179602939 |
| N2A | 3503 | 10732;10733;10734 | chr2:178738214;178738213;178738212 | chr2:179602941;179602940;179602939 |
| N2B | 4384 | 13375;13376;13377 | chr2:178738214;178738213;178738212 | chr2:179602941;179602940;179602939 |
| Novex-1 | 4509 | 13750;13751;13752 | chr2:178738214;178738213;178738212 | chr2:179602941;179602940;179602939 |
| Novex-2 | 4576 | 13951;13952;13953 | chr2:178738214;178738213;178738212 | chr2:179602941;179602940;179602939 |
| 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/C | rs1363033770  |
-0.654 | 0.997 | N | 0.4 | 0.359 | 0.42989457901 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs1363033770 |
-0.654 | 0.997 | N | 0.4 | 0.359 | 0.42989457901 | gnomAD-4.0.0 | 1.59156E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77932E-05 | None | 0 | 0 | 0 | 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 | 0.1015 | likely_benign | 0.1204 | benign | -0.857 | Destabilizing | 0.022 | N | 0.116 | neutral | N | 0.443383317 | None | None | N |
| S/C | 0.1826 | likely_benign | 0.217 | benign | -0.829 | Destabilizing | 0.997 | D | 0.4 | neutral | N | 0.444797087 | None | None | N |
| S/D | 0.6437 | likely_pathogenic | 0.7008 | pathogenic | -0.896 | Destabilizing | 0.842 | D | 0.298 | neutral | None | None | None | None | N |
| S/E | 0.74 | likely_pathogenic | 0.7667 | pathogenic | -0.868 | Destabilizing | 0.688 | D | 0.32 | neutral | None | None | None | None | N |
| S/F | 0.2256 | likely_benign | 0.3019 | benign | -1.041 | Destabilizing | 0.966 | D | 0.461 | neutral | N | 0.44464574 | None | None | N |
| S/G | 0.1807 | likely_benign | 0.228 | benign | -1.107 | Destabilizing | 0.688 | D | 0.302 | neutral | None | None | None | None | N |
| S/H | 0.4496 | ambiguous | 0.4549 | ambiguous | -1.525 | Destabilizing | 0.991 | D | 0.409 | neutral | None | None | None | None | N |
| S/I | 0.2004 | likely_benign | 0.2515 | benign | -0.286 | Destabilizing | 0.949 | D | 0.433 | neutral | None | None | None | None | N |
| S/K | 0.8309 | likely_pathogenic | 0.8364 | pathogenic | -0.705 | Destabilizing | 0.067 | N | 0.108 | neutral | None | None | None | None | N |
| S/L | 0.1129 | likely_benign | 0.1392 | benign | -0.286 | Destabilizing | 0.728 | D | 0.403 | neutral | None | None | None | None | N |
| S/M | 0.2618 | likely_benign | 0.3094 | benign | -0.026 | Destabilizing | 0.991 | D | 0.409 | neutral | None | None | None | None | N |
| S/N | 0.1981 | likely_benign | 0.2571 | benign | -0.836 | Destabilizing | 0.842 | D | 0.336 | neutral | None | None | None | None | N |
| S/P | 0.9013 | likely_pathogenic | 0.9301 | pathogenic | -0.444 | Destabilizing | 0.891 | D | 0.401 | neutral | N | 0.444432979 | None | None | N |
| S/Q | 0.655 | likely_pathogenic | 0.6574 | pathogenic | -1.04 | Destabilizing | 0.842 | D | 0.353 | neutral | None | None | None | None | N |
| S/R | 0.7198 | likely_pathogenic | 0.7339 | pathogenic | -0.588 | Destabilizing | 0.007 | N | 0.161 | neutral | None | None | None | None | N |
| S/T | 0.0986 | likely_benign | 0.1149 | benign | -0.803 | Destabilizing | 0.051 | N | 0.121 | neutral | N | 0.443703351 | None | None | N |
| S/V | 0.2071 | likely_benign | 0.2556 | benign | -0.444 | Destabilizing | 0.728 | D | 0.403 | neutral | None | None | None | None | N |
| S/W | 0.4551 | ambiguous | 0.5196 | ambiguous | -1.01 | Destabilizing | 0.998 | D | 0.521 | neutral | None | None | None | None | N |
| S/Y | 0.2287 | likely_benign | 0.2917 | benign | -0.713 | Destabilizing | 0.989 | D | 0.463 | neutral | N | 0.44464574 | 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.