Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20004 | 60235;60236;60237 | chr2:178591809;178591808;178591807 | chr2:179456536;179456535;179456534 |
| N2AB | 18363 | 55312;55313;55314 | chr2:178591809;178591808;178591807 | chr2:179456536;179456535;179456534 |
| N2A | 17436 | 52531;52532;52533 | chr2:178591809;178591808;178591807 | chr2:179456536;179456535;179456534 |
| N2B | 10939 | 33040;33041;33042 | chr2:178591809;178591808;178591807 | chr2:179456536;179456535;179456534 |
| Novex-1 | 11064 | 33415;33416;33417 | chr2:178591809;178591808;178591807 | chr2:179456536;179456535;179456534 |
| Novex-2 | 11131 | 33616;33617;33618 | chr2:178591809;178591808;178591807 | chr2:179456536;179456535;179456534 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1343530077  |
-0.748 | 0.978 | N | 0.56 | 0.378 | 0.407901774203 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/G | rs1343530077 |
-0.748 | 0.978 | N | 0.56 | 0.378 | 0.407901774203 | gnomAD-4.0.0 | 2.73763E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63833E-05 | 0 |
| D/N | None | None | 0.37 | N | 0.221 | 0.212 | 0.270001397563 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7477 | likely_pathogenic | 0.8205 | pathogenic | -0.497 | Destabilizing | 0.978 | D | 0.631 | neutral | N | 0.473636964 | None | None | I |
| D/C | 0.9481 | likely_pathogenic | 0.9679 | pathogenic | -0.068 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/E | 0.7485 | likely_pathogenic | 0.8064 | pathogenic | -0.651 | Destabilizing | 0.978 | D | 0.451 | neutral | D | 0.524868843 | None | None | I |
| D/F | 0.9558 | likely_pathogenic | 0.9683 | pathogenic | -0.508 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/G | 0.7423 | likely_pathogenic | 0.8008 | pathogenic | -0.775 | Destabilizing | 0.978 | D | 0.56 | neutral | N | 0.495730918 | None | None | I |
| D/H | 0.8468 | likely_pathogenic | 0.8948 | pathogenic | -0.851 | Destabilizing | 0.999 | D | 0.627 | neutral | N | 0.492501687 | None | None | I |
| D/I | 0.9117 | likely_pathogenic | 0.9439 | pathogenic | 0.209 | Stabilizing | 0.995 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/K | 0.9395 | likely_pathogenic | 0.9564 | pathogenic | -0.142 | Destabilizing | 0.995 | D | 0.571 | neutral | None | None | None | None | I |
| D/L | 0.8841 | likely_pathogenic | 0.912 | pathogenic | 0.209 | Stabilizing | 0.995 | D | 0.689 | prob.neutral | None | None | None | None | I |
| D/M | 0.9488 | likely_pathogenic | 0.966 | pathogenic | 0.645 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| D/N | 0.2002 | likely_benign | 0.2595 | benign | -0.444 | Destabilizing | 0.37 | N | 0.221 | neutral | N | 0.473480018 | None | None | I |
| D/P | 0.9565 | likely_pathogenic | 0.9582 | pathogenic | -0.002 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| D/Q | 0.9148 | likely_pathogenic | 0.9393 | pathogenic | -0.372 | Destabilizing | 0.998 | D | 0.603 | neutral | None | None | None | None | I |
| D/R | 0.9461 | likely_pathogenic | 0.9592 | pathogenic | -0.142 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/S | 0.442 | ambiguous | 0.5539 | ambiguous | -0.622 | Destabilizing | 0.967 | D | 0.529 | neutral | None | None | None | None | I |
| D/T | 0.5245 | ambiguous | 0.6332 | pathogenic | -0.399 | Destabilizing | 0.643 | D | 0.357 | neutral | None | None | None | None | I |
| D/V | 0.7896 | likely_pathogenic | 0.8539 | pathogenic | -0.002 | Destabilizing | 0.994 | D | 0.699 | prob.neutral | N | 0.484588422 | None | None | I |
| D/W | 0.9887 | likely_pathogenic | 0.9917 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| D/Y | 0.7384 | likely_pathogenic | 0.8144 | pathogenic | -0.289 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | D | 0.525191478 | None | None | I |
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.