Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2993 | 9202;9203;9204 | chr2:178768859;178768858;178768857 | chr2:179633586;179633585;179633584 |
| N2AB | 2993 | 9202;9203;9204 | chr2:178768859;178768858;178768857 | chr2:179633586;179633585;179633584 |
| N2A | 2993 | 9202;9203;9204 | chr2:178768859;178768858;178768857 | chr2:179633586;179633585;179633584 |
| N2B | 2947 | 9064;9065;9066 | chr2:178768859;178768858;178768857 | chr2:179633586;179633585;179633584 |
| Novex-1 | 2947 | 9064;9065;9066 | chr2:178768859;178768858;178768857 | chr2:179633586;179633585;179633584 |
| Novex-2 | 2947 | 9064;9065;9066 | chr2:178768859;178768858;178768857 | chr2:179633586;179633585;179633584 |
| Novex-3 | 2993 | 9202;9203;9204 | chr2:178768859;178768858;178768857 | chr2:179633586;179633585;179633584 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs772335542  |
-0.726 | 0.999 | N | 0.493 | 0.418 | 0.244539031024 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| N/S | rs772335542 |
-0.726 | 0.999 | N | 0.493 | 0.418 | 0.244539031024 | gnomAD-4.0.0 | 6.84097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.993E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9194 | likely_pathogenic | 0.9386 | pathogenic | -0.552 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| N/C | 0.9539 | likely_pathogenic | 0.961 | pathogenic | 0.07 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| N/D | 0.6425 | likely_pathogenic | 0.7118 | pathogenic | 0.004 | Stabilizing | 0.999 | D | 0.546 | neutral | D | 0.535853725 | None | None | N |
| N/E | 0.9807 | likely_pathogenic | 0.9842 | pathogenic | 0.083 | Stabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| N/F | 0.9955 | likely_pathogenic | 0.9959 | pathogenic | -0.555 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| N/G | 0.9003 | likely_pathogenic | 0.9248 | pathogenic | -0.84 | Destabilizing | 0.999 | D | 0.503 | neutral | None | None | None | None | N |
| N/H | 0.8746 | likely_pathogenic | 0.8979 | pathogenic | -0.568 | Destabilizing | 1.0 | D | 0.659 | neutral | D | 0.579939606 | None | None | N |
| N/I | 0.9555 | likely_pathogenic | 0.962 | pathogenic | 0.158 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | D | 0.577567415 | None | None | N |
| N/K | 0.989 | likely_pathogenic | 0.9921 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.673 | neutral | D | 0.531852093 | None | None | N |
| N/L | 0.948 | likely_pathogenic | 0.9529 | pathogenic | 0.158 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| N/M | 0.9645 | likely_pathogenic | 0.9704 | pathogenic | 0.226 | Stabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| N/P | 0.9606 | likely_pathogenic | 0.9712 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| N/Q | 0.9746 | likely_pathogenic | 0.9794 | pathogenic | -0.473 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| N/R | 0.9857 | likely_pathogenic | 0.9886 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| N/S | 0.2068 | likely_benign | 0.2251 | benign | -0.562 | Destabilizing | 0.999 | D | 0.493 | neutral | N | 0.417441242 | None | None | N |
| N/T | 0.5636 | ambiguous | 0.6198 | pathogenic | -0.297 | Destabilizing | 0.999 | D | 0.651 | neutral | N | 0.504254381 | None | None | N |
| N/V | 0.9559 | likely_pathogenic | 0.9618 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| N/W | 0.9986 | likely_pathogenic | 0.9988 | pathogenic | -0.452 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| N/Y | 0.9536 | likely_pathogenic | 0.957 | pathogenic | -0.174 | Destabilizing | 1.0 | D | 0.665 | neutral | D | 0.580087475 | 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.