Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14896 | 44911;44912;44913 | chr2:178624594;178624593;178624592 | chr2:179489321;179489320;179489319 |
| N2AB | 13255 | 39988;39989;39990 | chr2:178624594;178624593;178624592 | chr2:179489321;179489320;179489319 |
| N2A | 12328 | 37207;37208;37209 | chr2:178624594;178624593;178624592 | chr2:179489321;179489320;179489319 |
| N2B | 5831 | 17716;17717;17718 | chr2:178624594;178624593;178624592 | chr2:179489321;179489320;179489319 |
| Novex-1 | 5956 | 18091;18092;18093 | chr2:178624594;178624593;178624592 | chr2:179489321;179489320;179489319 |
| Novex-2 | 6023 | 18292;18293;18294 | chr2:178624594;178624593;178624592 | chr2:179489321;179489320;179489319 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs2058754432  |
None | 1.0 | N | 0.665 | 0.23 | 0.171388866994 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/N | rs2058754432 |
None | 1.0 | N | 0.665 | 0.23 | 0.171388866994 | gnomAD-4.0.0 | 6.58224E-06 | None | None | None | None | N | None | 2.41453E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs867080281 |
None | 0.999 | N | 0.529 | 0.26 | 0.256283259241 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 1.90042E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.3604 | ambiguous | 0.3975 | ambiguous | -0.078 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| K/C | 0.8702 | likely_pathogenic | 0.883 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| K/D | 0.4083 | ambiguous | 0.4379 | ambiguous | -0.312 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| K/E | 0.1542 | likely_benign | 0.1515 | benign | -0.332 | Destabilizing | 0.999 | D | 0.592 | neutral | N | 0.346373841 | None | None | N |
| K/F | 0.8904 | likely_pathogenic | 0.8988 | pathogenic | -0.484 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| K/G | 0.3979 | ambiguous | 0.4148 | ambiguous | -0.169 | Destabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | N |
| K/H | 0.4523 | ambiguous | 0.4869 | ambiguous | -0.249 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| K/I | 0.5578 | ambiguous | 0.5552 | ambiguous | 0.078 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| K/L | 0.4887 | ambiguous | 0.5086 | ambiguous | 0.078 | Stabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | N |
| K/M | 0.3982 | ambiguous | 0.3953 | ambiguous | -0.233 | Destabilizing | 1.0 | D | 0.639 | neutral | N | 0.406266756 | None | None | N |
| K/N | 0.3751 | ambiguous | 0.4042 | ambiguous | -0.152 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.336306485 | None | None | N |
| K/P | 0.4422 | ambiguous | 0.4891 | ambiguous | 0.046 | Stabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | N |
| K/Q | 0.17 | likely_benign | 0.1776 | benign | -0.267 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.324317827 | None | None | N |
| K/R | 0.1003 | likely_benign | 0.0981 | benign | -0.235 | Destabilizing | 0.999 | D | 0.529 | neutral | N | 0.343209243 | None | None | N |
| K/S | 0.377 | ambiguous | 0.42 | ambiguous | -0.499 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| K/T | 0.2331 | likely_benign | 0.2538 | benign | -0.416 | Destabilizing | 1.0 | D | 0.586 | neutral | N | 0.320494468 | None | None | N |
| K/V | 0.4894 | ambiguous | 0.493 | ambiguous | 0.046 | Stabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | N |
| K/W | 0.8689 | likely_pathogenic | 0.8638 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| K/Y | 0.8078 | likely_pathogenic | 0.8083 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.633 | 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.