Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2599 | 8020;8021;8022 | chr2:178773169;178773168;178773167 | chr2:179637896;179637895;179637894 |
| N2AB | 2599 | 8020;8021;8022 | chr2:178773169;178773168;178773167 | chr2:179637896;179637895;179637894 |
| N2A | 2599 | 8020;8021;8022 | chr2:178773169;178773168;178773167 | chr2:179637896;179637895;179637894 |
| N2B | 2553 | 7882;7883;7884 | chr2:178773169;178773168;178773167 | chr2:179637896;179637895;179637894 |
| Novex-1 | 2553 | 7882;7883;7884 | chr2:178773169;178773168;178773167 | chr2:179637896;179637895;179637894 |
| Novex-2 | 2553 | 7882;7883;7884 | chr2:178773169;178773168;178773167 | chr2:179637896;179637895;179637894 |
| Novex-3 | 2599 | 8020;8021;8022 | chr2:178773169;178773168;178773167 | chr2:179637896;179637895;179637894 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | rs2091784595  |
None | 1.0 | N | 0.775 | 0.618 | 0.594197360623 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| E/G | rs2091784595 |
None | 1.0 | N | 0.775 | 0.618 | 0.594197360623 | gnomAD-4.0.0 | 3.04488E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61491E-06 | 0 | 0 |
| E/V | rs2091784595 |
None | 1.0 | D | 0.826 | 0.597 | 0.673503988595 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/V | rs2091784595 |
None | 1.0 | D | 0.826 | 0.597 | 0.673503988595 | gnomAD-4.0.0 | 6.56996E-06 | None | None | None | None | N | None | 0 | 6.54707E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2429 | likely_benign | 0.2564 | benign | -0.674 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | N | 0.49069163 | None | None | N |
| E/C | 0.9692 | likely_pathogenic | 0.9713 | pathogenic | -0.271 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| E/D | 0.553 | ambiguous | 0.5856 | pathogenic | -0.871 | Destabilizing | 0.999 | D | 0.483 | neutral | D | 0.558377098 | None | None | N |
| E/F | 0.9746 | likely_pathogenic | 0.9727 | pathogenic | -0.424 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| E/G | 0.3914 | ambiguous | 0.3967 | ambiguous | -0.977 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.506690977 | None | None | N |
| E/H | 0.8968 | likely_pathogenic | 0.9009 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| E/I | 0.8352 | likely_pathogenic | 0.8033 | pathogenic | 0.128 | Stabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| E/K | 0.3771 | ambiguous | 0.3419 | ambiguous | -0.4 | Destabilizing | 0.999 | D | 0.59 | neutral | D | 0.586932393 | None | None | N |
| E/L | 0.8822 | likely_pathogenic | 0.8748 | pathogenic | 0.128 | Stabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| E/M | 0.7684 | likely_pathogenic | 0.7646 | pathogenic | 0.495 | Stabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| E/N | 0.7449 | likely_pathogenic | 0.7491 | pathogenic | -0.697 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| E/P | 0.9879 | likely_pathogenic | 0.9848 | pathogenic | -0.118 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| E/Q | 0.2613 | likely_benign | 0.2712 | benign | -0.616 | Destabilizing | 1.0 | D | 0.625 | neutral | D | 0.538753474 | None | None | N |
| E/R | 0.5985 | likely_pathogenic | 0.5775 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| E/S | 0.4155 | ambiguous | 0.4348 | ambiguous | -0.954 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | N |
| E/T | 0.5245 | ambiguous | 0.515 | ambiguous | -0.716 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| E/V | 0.636 | likely_pathogenic | 0.6031 | pathogenic | -0.118 | Destabilizing | 1.0 | D | 0.826 | deleterious | D | 0.538929011 | None | None | N |
| E/W | 0.9935 | likely_pathogenic | 0.9936 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| E/Y | 0.9586 | likely_pathogenic | 0.9588 | pathogenic | -0.203 | Destabilizing | 1.0 | D | 0.827 | deleterious | 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.