Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 10152 | 30679;30680;30681 | chr2:178702225;178702224;178702223 | chr2:179566952;179566951;179566950 |
| N2AB | 9835 | 29728;29729;29730 | chr2:178702225;178702224;178702223 | chr2:179566952;179566951;179566950 |
| N2A | 8908 | 26947;26948;26949 | chr2:178702225;178702224;178702223 | chr2:179566952;179566951;179566950 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs375796685  |
0.57 | 0.975 | None | 0.637 | 0.376 | 0.709553313446 | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | I | None | 0 | 1.15861E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/L | rs375796685 |
0.57 | 0.975 | None | 0.637 | 0.376 | 0.709553313446 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | rs375796685 |
0.57 | 0.975 | None | 0.637 | 0.376 | 0.709553313446 | gnomAD-4.0.0 | 6.19649E-06 | None | None | None | None | I | None | 0 | 1.00017E-04 | None | 0 | 0 | None | 0 | 0 | 8.47538E-07 | 0 | 4.80323E-05 |
| R/Q | rs375796685 |
0.056 | 0.998 | None | 0.709 | 0.295 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.42E-05 | 0 |
| R/Q | rs375796685 |
0.056 | 0.998 | None | 0.709 | 0.295 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs375796685 |
0.056 | 0.998 | None | 0.709 | 0.295 | None | gnomAD-4.0.0 | 1.42519E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.77983E-05 | 1.09789E-05 | 1.60108E-05 |
| R/W | rs1005491217 |
-0.589 | 1.0 | None | 0.762 | 0.345 | 0.473458370588 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| R/W | rs1005491217 |
-0.589 | 1.0 | None | 0.762 | 0.345 | 0.473458370588 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs1005491217 |
-0.589 | 1.0 | None | 0.762 | 0.345 | 0.473458370588 | gnomAD-4.0.0 | 9.29483E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.2713E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9378 | likely_pathogenic | 0.9416 | pathogenic | -1.003 | Destabilizing | 0.807 | D | 0.667 | neutral | None | None | None | None | I |
| R/C | 0.7411 | likely_pathogenic | 0.719 | pathogenic | -0.907 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | I |
| R/D | 0.9775 | likely_pathogenic | 0.9825 | pathogenic | -0.087 | Destabilizing | 0.986 | D | 0.625 | neutral | None | None | None | None | I |
| R/E | 0.8478 | likely_pathogenic | 0.8561 | pathogenic | 0.07 | Stabilizing | 0.953 | D | 0.696 | prob.neutral | None | None | None | None | I |
| R/F | 0.9453 | likely_pathogenic | 0.9471 | pathogenic | -0.566 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/G | 0.9264 | likely_pathogenic | 0.9289 | pathogenic | -1.355 | Destabilizing | 0.951 | D | 0.669 | neutral | None | None | None | None | I |
| R/H | 0.338 | likely_benign | 0.3287 | benign | -1.513 | Destabilizing | 0.998 | D | 0.719 | prob.delet. | None | None | None | None | I |
| R/I | 0.8062 | likely_pathogenic | 0.818 | pathogenic | -0.035 | Destabilizing | 0.993 | D | 0.71 | prob.delet. | None | None | None | None | I |
| R/K | 0.3585 | ambiguous | 0.3463 | ambiguous | -0.958 | Destabilizing | 0.893 | D | 0.56 | neutral | None | None | None | None | I |
| R/L | 0.7977 | likely_pathogenic | 0.8007 | pathogenic | -0.035 | Destabilizing | 0.975 | D | 0.637 | neutral | None | None | None | None | I |
| R/M | 0.8797 | likely_pathogenic | 0.8811 | pathogenic | -0.432 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | I |
| R/N | 0.9488 | likely_pathogenic | 0.9572 | pathogenic | -0.466 | Destabilizing | 0.953 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/P | 0.996 | likely_pathogenic | 0.9972 | pathogenic | -0.338 | Destabilizing | 0.996 | D | 0.712 | prob.delet. | None | None | None | None | I |
| R/Q | 0.3627 | ambiguous | 0.3389 | benign | -0.549 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/S | 0.914 | likely_pathogenic | 0.9196 | pathogenic | -1.299 | Destabilizing | 0.214 | N | 0.515 | neutral | None | None | None | None | I |
| R/T | 0.7939 | likely_pathogenic | 0.8072 | pathogenic | -0.944 | Destabilizing | 0.91 | D | 0.689 | prob.neutral | None | None | None | None | I |
| R/V | 0.8304 | likely_pathogenic | 0.8415 | pathogenic | -0.338 | Destabilizing | 0.986 | D | 0.71 | prob.delet. | None | None | None | None | I |
| R/W | 0.6983 | likely_pathogenic | 0.8649 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| R/Y | 0.8819 | likely_pathogenic | 0.8802 | pathogenic | 0.101 | Stabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | 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.