Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15687 | 47284;47285;47286 | chr2:178618399;178618398;178618397 | chr2:179483126;179483125;179483124 |
| N2AB | 14046 | 42361;42362;42363 | chr2:178618399;178618398;178618397 | chr2:179483126;179483125;179483124 |
| N2A | 13119 | 39580;39581;39582 | chr2:178618399;178618398;178618397 | chr2:179483126;179483125;179483124 |
| N2B | 6622 | 20089;20090;20091 | chr2:178618399;178618398;178618397 | chr2:179483126;179483125;179483124 |
| Novex-1 | 6747 | 20464;20465;20466 | chr2:178618399;178618398;178618397 | chr2:179483126;179483125;179483124 |
| Novex-2 | 6814 | 20665;20666;20667 | chr2:178618399;178618398;178618397 | chr2:179483126;179483125;179483124 |
| 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 | rs747113658  |
-1.111 | 0.994 | N | 0.587 | 0.259 | 0.274366138417 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/G | rs747113658 |
-1.111 | 0.994 | N | 0.587 | 0.259 | 0.274366138417 | gnomAD-4.0.0 | 1.59393E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43328E-05 | 0 |
| S/N | rs2057732244 |
None | 0.994 | D | 0.683 | 0.347 | 0.302793454619 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/N | rs2057732244 |
None | 0.994 | D | 0.683 | 0.347 | 0.302793454619 | gnomAD-4.0.0 | 2.48089E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.3924E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.228 | likely_benign | 0.2333 | benign | -0.648 | Destabilizing | 0.98 | D | 0.589 | neutral | None | None | None | None | I |
| S/C | 0.2236 | likely_benign | 0.2911 | benign | -0.488 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | D | 0.557864577 | None | None | I |
| S/D | 0.8497 | likely_pathogenic | 0.8543 | pathogenic | -0.503 | Destabilizing | 0.996 | D | 0.68 | prob.neutral | None | None | None | None | I |
| S/E | 0.9165 | likely_pathogenic | 0.8652 | pathogenic | -0.543 | Destabilizing | 0.996 | D | 0.67 | neutral | None | None | None | None | I |
| S/F | 0.8931 | likely_pathogenic | 0.8425 | pathogenic | -1.003 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| S/G | 0.3786 | ambiguous | 0.3564 | ambiguous | -0.846 | Destabilizing | 0.994 | D | 0.587 | neutral | N | 0.520961904 | None | None | I |
| S/H | 0.8978 | likely_pathogenic | 0.8559 | pathogenic | -1.393 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/I | 0.8649 | likely_pathogenic | 0.8227 | pathogenic | -0.238 | Destabilizing | 0.997 | D | 0.737 | prob.delet. | D | 0.658407468 | None | None | I |
| S/K | 0.9918 | likely_pathogenic | 0.9836 | pathogenic | -0.753 | Destabilizing | 0.996 | D | 0.675 | prob.neutral | None | None | None | None | I |
| S/L | 0.6158 | likely_pathogenic | 0.5558 | ambiguous | -0.238 | Destabilizing | 0.992 | D | 0.673 | neutral | None | None | None | None | I |
| S/M | 0.6849 | likely_pathogenic | 0.6509 | pathogenic | 0.187 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/N | 0.6418 | likely_pathogenic | 0.6115 | pathogenic | -0.646 | Destabilizing | 0.994 | D | 0.683 | prob.neutral | D | 0.614653316 | None | None | I |
| S/P | 0.9918 | likely_pathogenic | 0.9887 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| S/Q | 0.9189 | likely_pathogenic | 0.8737 | pathogenic | -0.92 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| S/R | 0.9854 | likely_pathogenic | 0.9731 | pathogenic | -0.537 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | D | 0.588009364 | None | None | I |
| S/T | 0.26 | likely_benign | 0.2399 | benign | -0.675 | Destabilizing | 0.543 | D | 0.507 | neutral | D | 0.526722499 | None | None | I |
| S/V | 0.7469 | likely_pathogenic | 0.7128 | pathogenic | -0.343 | Destabilizing | 0.998 | D | 0.708 | prob.delet. | None | None | None | None | I |
| S/W | 0.9058 | likely_pathogenic | 0.881 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| S/Y | 0.8272 | likely_pathogenic | 0.7444 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.732 | 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.