Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2829 | 8710;8711;8712 | chr2:178770216;178770215;178770214 | chr2:179634943;179634942;179634941 |
| N2AB | 2829 | 8710;8711;8712 | chr2:178770216;178770215;178770214 | chr2:179634943;179634942;179634941 |
| N2A | 2829 | 8710;8711;8712 | chr2:178770216;178770215;178770214 | chr2:179634943;179634942;179634941 |
| N2B | 2783 | 8572;8573;8574 | chr2:178770216;178770215;178770214 | chr2:179634943;179634942;179634941 |
| Novex-1 | 2783 | 8572;8573;8574 | chr2:178770216;178770215;178770214 | chr2:179634943;179634942;179634941 |
| Novex-2 | 2783 | 8572;8573;8574 | chr2:178770216;178770215;178770214 | chr2:179634943;179634942;179634941 |
| Novex-3 | 2829 | 8710;8711;8712 | chr2:178770216;178770215;178770214 | chr2:179634943;179634942;179634941 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | rs1272480712  |
-0.054 | 0.042 | N | 0.493 | 0.279 | 0.411401001288 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| H/L | rs1272480712 |
-0.054 | 0.042 | N | 0.493 | 0.279 | 0.411401001288 | gnomAD-4.0.0 | 1.02609E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25901E-05 | 0 | 1.65574E-05 |
| H/R | None | None | 0.602 | N | 0.633 | 0.253 | 0.119812018005 | gnomAD-4.0.0 | 6.84063E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.6962 | likely_pathogenic | 0.7974 | pathogenic | -1.152 | Destabilizing | 0.104 | N | 0.553 | neutral | None | None | None | None | N |
| H/C | 0.2252 | likely_benign | 0.2817 | benign | -0.411 | Destabilizing | 0.958 | D | 0.699 | prob.neutral | None | None | None | None | N |
| H/D | 0.7272 | likely_pathogenic | 0.802 | pathogenic | -0.745 | Destabilizing | 0.301 | N | 0.653 | neutral | N | 0.430619147 | None | None | N |
| H/E | 0.7261 | likely_pathogenic | 0.804 | pathogenic | -0.595 | Destabilizing | 0.364 | N | 0.583 | neutral | None | None | None | None | N |
| H/F | 0.3646 | ambiguous | 0.4323 | ambiguous | 0.348 | Stabilizing | None | N | 0.309 | neutral | None | None | None | None | N |
| H/G | 0.7563 | likely_pathogenic | 0.8293 | pathogenic | -1.56 | Destabilizing | 0.364 | N | 0.625 | neutral | None | None | None | None | N |
| H/I | 0.5823 | likely_pathogenic | 0.6947 | pathogenic | 0.011 | Stabilizing | 0.124 | N | 0.645 | neutral | None | None | None | None | N |
| H/K | 0.499 | ambiguous | 0.5539 | ambiguous | -0.629 | Destabilizing | 0.22 | N | 0.637 | neutral | None | None | None | None | N |
| H/L | 0.2227 | likely_benign | 0.293 | benign | 0.011 | Stabilizing | 0.042 | N | 0.493 | neutral | N | 0.431218009 | None | None | N |
| H/M | 0.7318 | likely_pathogenic | 0.8157 | pathogenic | -0.232 | Destabilizing | 0.667 | D | 0.678 | prob.neutral | None | None | None | None | N |
| H/N | 0.3024 | likely_benign | 0.3938 | ambiguous | -0.991 | Destabilizing | 0.301 | N | 0.607 | neutral | N | 0.430619147 | None | None | N |
| H/P | 0.8863 | likely_pathogenic | 0.9167 | pathogenic | -0.359 | Destabilizing | 0.822 | D | 0.687 | prob.neutral | N | 0.430619147 | None | None | N |
| H/Q | 0.325 | likely_benign | 0.4158 | ambiguous | -0.675 | Destabilizing | 0.602 | D | 0.629 | neutral | N | 0.44689616 | None | None | N |
| H/R | 0.1845 | likely_benign | 0.2143 | benign | -0.937 | Destabilizing | 0.602 | D | 0.633 | neutral | N | 0.41163642 | None | None | N |
| H/S | 0.561 | ambiguous | 0.6756 | pathogenic | -1.157 | Destabilizing | 0.22 | N | 0.628 | neutral | None | None | None | None | N |
| H/T | 0.7421 | likely_pathogenic | 0.8406 | pathogenic | -0.889 | Destabilizing | 0.364 | N | 0.645 | neutral | None | None | None | None | N |
| H/V | 0.5217 | ambiguous | 0.6291 | pathogenic | -0.359 | Destabilizing | 0.22 | N | 0.618 | neutral | None | None | None | None | N |
| H/W | 0.4364 | ambiguous | 0.4973 | ambiguous | 0.817 | Stabilizing | 0.667 | D | 0.677 | prob.neutral | None | None | None | None | N |
| H/Y | 0.1019 | likely_benign | 0.1203 | benign | 0.821 | Stabilizing | None | N | 0.169 | neutral | N | 0.448876241 | 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.