Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3048 | 9367;9368;9369 | chr2:178768694;178768693;178768692 | chr2:179633421;179633420;179633419 |
| N2AB | 3048 | 9367;9368;9369 | chr2:178768694;178768693;178768692 | chr2:179633421;179633420;179633419 |
| N2A | 3048 | 9367;9368;9369 | chr2:178768694;178768693;178768692 | chr2:179633421;179633420;179633419 |
| N2B | 3002 | 9229;9230;9231 | chr2:178768694;178768693;178768692 | chr2:179633421;179633420;179633419 |
| Novex-1 | 3002 | 9229;9230;9231 | chr2:178768694;178768693;178768692 | chr2:179633421;179633420;179633419 |
| Novex-2 | 3002 | 9229;9230;9231 | chr2:178768694;178768693;178768692 | chr2:179633421;179633420;179633419 |
| Novex-3 | 3048 | 9367;9368;9369 | chr2:178768694;178768693;178768692 | chr2:179633421;179633420;179633419 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs74773630  |
None | 0.022 | N | 0.214 | 0.164 | 0.208000267992 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs74773630 |
None | 0.022 | N | 0.214 | 0.164 | 0.208000267992 | gnomAD-4.0.0 | 3.84454E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17648E-06 | 0 | 0 |
| T/P | rs74773630 |
-0.541 | 0.966 | D | 0.611 | 0.491 | None | gnomAD-4.0.0 | 4.68102E-04 | None | None | None | None | N | None | 1.13071E-04 | 2.28697E-05 | None | 0 | 0 | None | 4.07722E-03 | 4.82625E-04 | 1.11434E-04 | 0 | 1.06048E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0997 | likely_benign | 0.0985 | benign | -0.808 | Destabilizing | 0.022 | N | 0.214 | neutral | N | 0.510637132 | None | None | N |
| T/C | 0.5056 | ambiguous | 0.5452 | ambiguous | -0.452 | Destabilizing | 0.998 | D | 0.58 | neutral | None | None | None | None | N |
| T/D | 0.5921 | likely_pathogenic | 0.6212 | pathogenic | -0.172 | Destabilizing | 0.842 | D | 0.56 | neutral | None | None | None | None | N |
| T/E | 0.422 | ambiguous | 0.4217 | ambiguous | -0.228 | Destabilizing | 0.728 | D | 0.55 | neutral | None | None | None | None | N |
| T/F | 0.4127 | ambiguous | 0.406 | ambiguous | -1.297 | Destabilizing | 0.991 | D | 0.636 | neutral | None | None | None | None | N |
| T/G | 0.3876 | ambiguous | 0.4127 | ambiguous | -0.956 | Destabilizing | 0.525 | D | 0.531 | neutral | None | None | None | None | N |
| T/H | 0.2898 | likely_benign | 0.3139 | benign | -1.387 | Destabilizing | 0.998 | D | 0.611 | neutral | None | None | None | None | N |
| T/I | 0.2797 | likely_benign | 0.2759 | benign | -0.519 | Destabilizing | 0.966 | D | 0.615 | neutral | D | 0.5482236 | None | None | N |
| T/K | 0.1923 | likely_benign | 0.2073 | benign | -0.463 | Destabilizing | 0.012 | N | 0.319 | neutral | N | 0.489070572 | None | None | N |
| T/L | 0.2047 | likely_benign | 0.1932 | benign | -0.519 | Destabilizing | 0.842 | D | 0.549 | neutral | None | None | None | None | N |
| T/M | 0.1174 | likely_benign | 0.1085 | benign | -0.032 | Destabilizing | 0.991 | D | 0.593 | neutral | None | None | None | None | N |
| T/N | 0.1849 | likely_benign | 0.203 | benign | -0.299 | Destabilizing | 0.842 | D | 0.559 | neutral | None | None | None | None | N |
| T/P | 0.5929 | likely_pathogenic | 0.6159 | pathogenic | -0.588 | Destabilizing | 0.966 | D | 0.611 | neutral | D | 0.591732706 | None | None | N |
| T/Q | 0.2509 | likely_benign | 0.2508 | benign | -0.638 | Destabilizing | 0.949 | D | 0.623 | neutral | None | None | None | None | N |
| T/R | 0.1731 | likely_benign | 0.1706 | benign | -0.188 | Destabilizing | 0.669 | D | 0.592 | neutral | N | 0.505154715 | None | None | N |
| T/S | 0.1146 | likely_benign | 0.1228 | benign | -0.566 | Destabilizing | 0.022 | N | 0.232 | neutral | N | 0.44759321 | None | None | N |
| T/V | 0.1857 | likely_benign | 0.1792 | benign | -0.588 | Destabilizing | 0.842 | D | 0.51 | neutral | None | None | None | None | N |
| T/W | 0.808 | likely_pathogenic | 0.7911 | pathogenic | -1.189 | Destabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| T/Y | 0.454 | ambiguous | 0.4754 | ambiguous | -0.927 | Destabilizing | 0.991 | D | 0.633 | 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.