Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15444 | 46555;46556;46557 | chr2:178620087;178620086;178620085 | chr2:179484814;179484813;179484812 |
| N2AB | 13803 | 41632;41633;41634 | chr2:178620087;178620086;178620085 | chr2:179484814;179484813;179484812 |
| N2A | 12876 | 38851;38852;38853 | chr2:178620087;178620086;178620085 | chr2:179484814;179484813;179484812 |
| N2B | 6379 | 19360;19361;19362 | chr2:178620087;178620086;178620085 | chr2:179484814;179484813;179484812 |
| Novex-1 | 6504 | 19735;19736;19737 | chr2:178620087;178620086;178620085 | chr2:179484814;179484813;179484812 |
| Novex-2 | 6571 | 19936;19937;19938 | chr2:178620087;178620086;178620085 | chr2:179484814;179484813;179484812 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs1333036641  |
-1.227 | None | N | 0.109 | 0.126 | 0.310458034454 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.64E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1333036641 |
-1.227 | None | N | 0.109 | 0.126 | 0.310458034454 | gnomAD-4.0.0 | 1.59876E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78583E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1971 | likely_benign | 0.3711 | ambiguous | -1.718 | Destabilizing | 0.007 | N | 0.329 | neutral | None | None | None | None | N |
| I/C | 0.4637 | ambiguous | 0.627 | pathogenic | -0.945 | Destabilizing | 0.356 | N | 0.493 | neutral | None | None | None | None | N |
| I/D | 0.4714 | ambiguous | 0.6864 | pathogenic | -1.738 | Destabilizing | 0.072 | N | 0.624 | neutral | None | None | None | None | N |
| I/E | 0.3152 | likely_benign | 0.5045 | ambiguous | -1.771 | Destabilizing | 0.072 | N | 0.618 | neutral | None | None | None | None | N |
| I/F | 0.1272 | likely_benign | 0.1593 | benign | -1.436 | Destabilizing | None | N | 0.154 | neutral | None | None | None | None | N |
| I/G | 0.4318 | ambiguous | 0.6643 | pathogenic | -2.007 | Highly Destabilizing | 0.072 | N | 0.581 | neutral | None | None | None | None | N |
| I/H | 0.2439 | likely_benign | 0.3641 | ambiguous | -1.279 | Destabilizing | 0.628 | D | 0.589 | neutral | None | None | None | None | N |
| I/K | 0.1838 | likely_benign | 0.2795 | benign | -1.088 | Destabilizing | 0.055 | N | 0.617 | neutral | N | 0.444137673 | None | None | N |
| I/L | 0.0875 | likely_benign | 0.1108 | benign | -0.996 | Destabilizing | None | N | 0.104 | neutral | N | 0.476297567 | None | None | N |
| I/M | 0.0971 | likely_benign | 0.121 | benign | -0.62 | Destabilizing | None | N | 0.155 | neutral | N | 0.477222226 | None | None | N |
| I/N | 0.1466 | likely_benign | 0.2394 | benign | -0.866 | Destabilizing | 0.072 | N | 0.625 | neutral | None | None | None | None | N |
| I/P | 0.8836 | likely_pathogenic | 0.956 | pathogenic | -1.207 | Destabilizing | 0.136 | N | 0.64 | neutral | None | None | None | None | N |
| I/Q | 0.2076 | likely_benign | 0.3412 | ambiguous | -1.156 | Destabilizing | 0.356 | N | 0.626 | neutral | None | None | None | None | N |
| I/R | 0.1588 | likely_benign | 0.2264 | benign | -0.428 | Destabilizing | 0.055 | N | 0.629 | neutral | N | 0.473016192 | None | None | N |
| I/S | 0.156 | likely_benign | 0.2757 | benign | -1.372 | Destabilizing | 0.016 | N | 0.497 | neutral | None | None | None | None | N |
| I/T | 0.1012 | likely_benign | 0.1721 | benign | -1.304 | Destabilizing | None | N | 0.146 | neutral | N | 0.436969089 | None | None | N |
| I/V | 0.0792 | likely_benign | 0.0771 | benign | -1.207 | Destabilizing | None | N | 0.109 | neutral | N | 0.416283759 | None | None | N |
| I/W | 0.5506 | ambiguous | 0.6953 | pathogenic | -1.505 | Destabilizing | 0.864 | D | 0.573 | neutral | None | None | None | None | N |
| I/Y | 0.302 | likely_benign | 0.404 | ambiguous | -1.279 | Destabilizing | 0.038 | N | 0.542 | 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.