Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2358 | 7297;7298;7299 | chr2:178774096;178774095;178774094 | chr2:179638823;179638822;179638821 |
| N2AB | 2358 | 7297;7298;7299 | chr2:178774096;178774095;178774094 | chr2:179638823;179638822;179638821 |
| N2A | 2358 | 7297;7298;7299 | chr2:178774096;178774095;178774094 | chr2:179638823;179638822;179638821 |
| N2B | 2312 | 7159;7160;7161 | chr2:178774096;178774095;178774094 | chr2:179638823;179638822;179638821 |
| Novex-1 | 2312 | 7159;7160;7161 | chr2:178774096;178774095;178774094 | chr2:179638823;179638822;179638821 |
| Novex-2 | 2312 | 7159;7160;7161 | chr2:178774096;178774095;178774094 | chr2:179638823;179638822;179638821 |
| Novex-3 | 2358 | 7297;7298;7299 | chr2:178774096;178774095;178774094 | chr2:179638823;179638822;179638821 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1175538754  |
None | 0.005 | N | 0.247 | 0.251 | 0.549839970675 | gnomAD-4.0.0 | 2.05229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69793E-06 | 0 | 0 |
| I/M | rs753536718 |
-0.574 | 0.976 | D | 0.486 | 0.485 | 0.563655836063 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/M | rs753536718 |
-0.574 | 0.976 | D | 0.486 | 0.485 | 0.563655836063 | gnomAD-4.0.0 | 1.59073E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| I/V | rs1175538754 |
-0.476 | 0.509 | N | 0.365 | 0.223 | 0.662238901992 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1175538754 |
-0.476 | 0.509 | N | 0.365 | 0.223 | 0.662238901992 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 1.30907E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1175538754 |
-0.476 | 0.509 | N | 0.365 | 0.223 | 0.662238901992 | gnomAD-4.0.0 | 1.85876E-06 | None | None | None | None | N | None | 0 | 3.33378E-05 | None | 0 | 0 | None | 0 | 0 | 8.47462E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9055 | likely_pathogenic | 0.9095 | pathogenic | -1.414 | Destabilizing | 0.927 | D | 0.477 | neutral | None | None | None | None | N |
| I/C | 0.9599 | likely_pathogenic | 0.9585 | pathogenic | -1.027 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| I/D | 0.9935 | likely_pathogenic | 0.994 | pathogenic | -0.495 | Destabilizing | 0.997 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/E | 0.9867 | likely_pathogenic | 0.9879 | pathogenic | -0.459 | Destabilizing | 0.997 | D | 0.653 | neutral | None | None | None | None | N |
| I/F | 0.3747 | ambiguous | 0.3822 | ambiguous | -0.804 | Destabilizing | 0.976 | D | 0.459 | neutral | N | 0.479990494 | None | None | N |
| I/G | 0.9857 | likely_pathogenic | 0.9867 | pathogenic | -1.762 | Destabilizing | 0.997 | D | 0.655 | neutral | None | None | None | None | N |
| I/H | 0.9733 | likely_pathogenic | 0.974 | pathogenic | -0.93 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/K | 0.9644 | likely_pathogenic | 0.9667 | pathogenic | -0.944 | Destabilizing | 0.997 | D | 0.647 | neutral | None | None | None | None | N |
| I/L | 0.1966 | likely_benign | 0.2019 | benign | -0.532 | Destabilizing | 0.005 | N | 0.247 | neutral | N | 0.483421845 | None | None | N |
| I/M | 0.2646 | likely_benign | 0.2728 | benign | -0.557 | Destabilizing | 0.976 | D | 0.486 | neutral | D | 0.627667618 | None | None | N |
| I/N | 0.9343 | likely_pathogenic | 0.9382 | pathogenic | -0.86 | Destabilizing | 0.996 | D | 0.681 | prob.neutral | D | 0.630840899 | None | None | N |
| I/P | 0.9583 | likely_pathogenic | 0.9645 | pathogenic | -0.794 | Destabilizing | 0.997 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/Q | 0.9703 | likely_pathogenic | 0.9722 | pathogenic | -0.939 | Destabilizing | 0.997 | D | 0.684 | prob.neutral | None | None | None | None | N |
| I/R | 0.9521 | likely_pathogenic | 0.953 | pathogenic | -0.486 | Destabilizing | 0.997 | D | 0.676 | prob.neutral | None | None | None | None | N |
| I/S | 0.9372 | likely_pathogenic | 0.94 | pathogenic | -1.552 | Destabilizing | 0.996 | D | 0.613 | neutral | D | 0.630009141 | None | None | N |
| I/T | 0.9105 | likely_pathogenic | 0.916 | pathogenic | -1.388 | Destabilizing | 0.959 | D | 0.525 | neutral | D | 0.629527687 | None | None | N |
| I/V | 0.1039 | likely_benign | 0.1049 | benign | -0.794 | Destabilizing | 0.509 | D | 0.365 | neutral | N | 0.506958471 | None | None | N |
| I/W | 0.9695 | likely_pathogenic | 0.9695 | pathogenic | -0.886 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/Y | 0.8976 | likely_pathogenic | 0.8975 | pathogenic | -0.641 | Destabilizing | 0.997 | D | 0.526 | 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.