Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25162 | 75709;75710;75711 | chr2:178570648;178570647;178570646 | chr2:179435375;179435374;179435373 |
| N2AB | 23521 | 70786;70787;70788 | chr2:178570648;178570647;178570646 | chr2:179435375;179435374;179435373 |
| N2A | 22594 | 68005;68006;68007 | chr2:178570648;178570647;178570646 | chr2:179435375;179435374;179435373 |
| N2B | 16097 | 48514;48515;48516 | chr2:178570648;178570647;178570646 | chr2:179435375;179435374;179435373 |
| Novex-1 | 16222 | 48889;48890;48891 | chr2:178570648;178570647;178570646 | chr2:179435375;179435374;179435373 |
| Novex-2 | 16289 | 49090;49091;49092 | chr2:178570648;178570647;178570646 | chr2:179435375;179435374;179435373 |
| 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/G | rs889930941  |
-0.612 | 0.454 | N | 0.453 | 0.174 | 0.222439326576 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| S/N | None | None | 0.002 | N | 0.241 | 0.094 | 0.151104730317 | gnomAD-4.0.0 | 6.84335E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99577E-07 | 0 | 0 |
| S/T | rs750324994 |
0.026 | 0.051 | N | 0.235 | 0.098 | 0.166414681773 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65837E-04 |
| S/T | rs750324994 |
0.026 | 0.051 | N | 0.235 | 0.098 | 0.166414681773 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 2.62226E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs750324994 |
0.026 | 0.051 | N | 0.235 | 0.098 | 0.166414681773 | gnomAD-4.0.0 | 6.81768E-06 | None | None | None | None | N | None | 1.3334E-05 | 1.33378E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20246E-05 |
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 | 0.1006 | likely_benign | 0.1031 | benign | -0.37 | Destabilizing | 0.525 | D | 0.457 | neutral | None | None | None | None | N |
| S/C | 0.1131 | likely_benign | 0.1197 | benign | -0.231 | Destabilizing | 0.997 | D | 0.497 | neutral | N | 0.494455422 | None | None | N |
| S/D | 0.3558 | ambiguous | 0.3133 | benign | 0.3 | Stabilizing | 0.728 | D | 0.389 | neutral | None | None | None | None | N |
| S/E | 0.474 | ambiguous | 0.4596 | ambiguous | 0.2 | Stabilizing | 0.842 | D | 0.407 | neutral | None | None | None | None | N |
| S/F | 0.2528 | likely_benign | 0.305 | benign | -1.012 | Destabilizing | 0.974 | D | 0.573 | neutral | None | None | None | None | N |
| S/G | 0.1094 | likely_benign | 0.0959 | benign | -0.464 | Destabilizing | 0.454 | N | 0.453 | neutral | N | 0.508931891 | None | None | N |
| S/H | 0.3307 | likely_benign | 0.3324 | benign | -1.023 | Destabilizing | 0.974 | D | 0.507 | neutral | None | None | None | None | N |
| S/I | 0.2003 | likely_benign | 0.2075 | benign | -0.255 | Destabilizing | 0.934 | D | 0.565 | neutral | N | 0.513972351 | None | None | N |
| S/K | 0.6234 | likely_pathogenic | 0.6124 | pathogenic | -0.361 | Destabilizing | 0.842 | D | 0.407 | neutral | None | None | None | None | N |
| S/L | 0.1312 | likely_benign | 0.1562 | benign | -0.255 | Destabilizing | 0.728 | D | 0.503 | neutral | None | None | None | None | N |
| S/M | 0.1766 | likely_benign | 0.2055 | benign | 0.019 | Stabilizing | 0.998 | D | 0.493 | neutral | None | None | None | None | N |
| S/N | 0.0996 | likely_benign | 0.0863 | benign | -0.078 | Destabilizing | 0.002 | N | 0.241 | neutral | N | 0.394318306 | None | None | N |
| S/P | 0.5419 | ambiguous | 0.5697 | pathogenic | -0.266 | Destabilizing | 0.974 | D | 0.487 | neutral | None | None | None | None | N |
| S/Q | 0.4775 | ambiguous | 0.4648 | ambiguous | -0.335 | Destabilizing | 0.974 | D | 0.496 | neutral | None | None | None | None | N |
| S/R | 0.6043 | likely_pathogenic | 0.5945 | pathogenic | -0.209 | Destabilizing | 0.934 | D | 0.468 | neutral | N | 0.485073596 | None | None | N |
| S/T | 0.0699 | likely_benign | 0.0747 | benign | -0.206 | Destabilizing | 0.051 | N | 0.235 | neutral | N | 0.441437462 | None | None | N |
| S/V | 0.197 | likely_benign | 0.2126 | benign | -0.266 | Destabilizing | 0.728 | D | 0.539 | neutral | None | None | None | None | N |
| S/W | 0.3999 | ambiguous | 0.4772 | ambiguous | -1.015 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | N |
| S/Y | 0.166 | likely_benign | 0.2033 | benign | -0.727 | Destabilizing | 0.991 | D | 0.575 | 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.