Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25064 | 75415;75416;75417 | chr2:178570942;178570941;178570940 | chr2:179435669;179435668;179435667 |
| N2AB | 23423 | 70492;70493;70494 | chr2:178570942;178570941;178570940 | chr2:179435669;179435668;179435667 |
| N2A | 22496 | 67711;67712;67713 | chr2:178570942;178570941;178570940 | chr2:179435669;179435668;179435667 |
| N2B | 15999 | 48220;48221;48222 | chr2:178570942;178570941;178570940 | chr2:179435669;179435668;179435667 |
| Novex-1 | 16124 | 48595;48596;48597 | chr2:178570942;178570941;178570940 | chr2:179435669;179435668;179435667 |
| Novex-2 | 16191 | 48796;48797;48798 | chr2:178570942;178570941;178570940 | chr2:179435669;179435668;179435667 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs893428451  |
-0.816 | 0.656 | N | 0.423 | 0.297 | 0.228597637076 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/A | rs893428451 |
-0.816 | 0.656 | N | 0.423 | 0.297 | 0.228597637076 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/A | rs893428451 |
-0.816 | 0.656 | N | 0.423 | 0.297 | 0.228597637076 | gnomAD-4.0.0 | 2.85118E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.81481E-05 | 0 | 1.60149E-05 |
| T/P | None | None | 0.99 | N | 0.619 | 0.519 | 0.480724696071 | gnomAD-4.0.0 | 6.84284E-07 | None | None | None | None | N | None | 0 | 2.23614E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1363 | likely_benign | 0.1286 | benign | -0.777 | Destabilizing | 0.656 | D | 0.423 | neutral | N | 0.478841204 | None | None | N |
| T/C | 0.2645 | likely_benign | 0.2528 | benign | -0.55 | Destabilizing | 0.092 | N | 0.352 | neutral | None | None | None | None | N |
| T/D | 0.5549 | ambiguous | 0.5187 | ambiguous | -1.318 | Destabilizing | 0.978 | D | 0.603 | neutral | None | None | None | None | N |
| T/E | 0.4226 | ambiguous | 0.4049 | ambiguous | -1.132 | Destabilizing | 0.956 | D | 0.573 | neutral | None | None | None | None | N |
| T/F | 0.5287 | ambiguous | 0.4854 | ambiguous | -0.464 | Destabilizing | 0.993 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/G | 0.3322 | likely_benign | 0.3032 | benign | -1.18 | Destabilizing | 0.956 | D | 0.586 | neutral | None | None | None | None | N |
| T/H | 0.3575 | ambiguous | 0.338 | benign | -1.362 | Destabilizing | 0.994 | D | 0.673 | neutral | None | None | None | None | N |
| T/I | 0.3643 | ambiguous | 0.3462 | ambiguous | 0.274 | Stabilizing | 0.97 | D | 0.614 | neutral | N | 0.50714013 | None | None | N |
| T/K | 0.326 | likely_benign | 0.3079 | benign | -0.595 | Destabilizing | 0.754 | D | 0.525 | neutral | None | None | None | None | N |
| T/L | 0.11 | likely_benign | 0.1066 | benign | 0.274 | Stabilizing | 0.86 | D | 0.455 | neutral | None | None | None | None | N |
| T/M | 0.1142 | likely_benign | 0.1115 | benign | 0.177 | Stabilizing | 0.998 | D | 0.624 | neutral | None | None | None | None | N |
| T/N | 0.1164 | likely_benign | 0.1071 | benign | -1.221 | Destabilizing | 0.942 | D | 0.489 | neutral | N | 0.520985963 | None | None | N |
| T/P | 0.2012 | likely_benign | 0.1763 | benign | -0.045 | Destabilizing | 0.99 | D | 0.619 | neutral | N | 0.519119094 | None | None | N |
| T/Q | 0.3121 | likely_benign | 0.2921 | benign | -0.964 | Destabilizing | 0.956 | D | 0.629 | neutral | None | None | None | None | N |
| T/R | 0.2426 | likely_benign | 0.2323 | benign | -0.791 | Destabilizing | 0.043 | N | 0.331 | neutral | None | None | None | None | N |
| T/S | 0.1554 | likely_benign | 0.141 | benign | -1.389 | Destabilizing | 0.822 | D | 0.421 | neutral | N | 0.493844814 | None | None | N |
| T/V | 0.2538 | likely_benign | 0.2438 | benign | -0.045 | Destabilizing | 0.86 | D | 0.417 | neutral | None | None | None | None | N |
| T/W | 0.863 | likely_pathogenic | 0.8326 | pathogenic | -0.746 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| T/Y | 0.5061 | ambiguous | 0.4597 | ambiguous | -0.326 | Destabilizing | 0.993 | D | 0.675 | prob.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.