Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14571 | 43936;43937;43938 | chr2:178632183;178632182;178632181 | chr2:179496910;179496909;179496908 |
| N2AB | 12930 | 39013;39014;39015 | chr2:178632183;178632182;178632181 | chr2:179496910;179496909;179496908 |
| N2A | 12003 | 36232;36233;36234 | chr2:178632183;178632182;178632181 | chr2:179496910;179496909;179496908 |
| N2B | 5506 | 16741;16742;16743 | chr2:178632183;178632182;178632181 | chr2:179496910;179496909;179496908 |
| Novex-1 | 5631 | 17116;17117;17118 | chr2:178632183;178632182;178632181 | chr2:179496910;179496909;179496908 |
| Novex-2 | 5698 | 17317;17318;17319 | chr2:178632183;178632182;178632181 | chr2:179496910;179496909;179496908 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | None | None | 0.005 | N | 0.171 | 0.192 | 0.580864329964 | gnomAD-4.0.0 | 6.86579E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01448E-07 | 0 | 0 |
| M/T | rs910523235  |
None | 0.959 | N | 0.453 | 0.387 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/T | rs910523235 |
None | 0.959 | N | 0.453 | 0.387 | None | gnomAD-4.0.0 | 2.23789E-05 | None | None | None | None | N | None | 1.33626E-05 | 1.68203E-05 | None | 0 | 0 | None | 0 | 0 | 2.80286E-05 | 0 | 1.60576E-05 |
| M/V | rs373801238 |
0.112 | 0.704 | N | 0.379 | 0.174 | None | gnomAD-2.1.1 | 1.25E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.76E-05 | 0 |
| M/V | rs373801238 |
0.112 | 0.704 | N | 0.379 | 0.174 | None | 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 |
| M/V | rs373801238 |
0.112 | 0.704 | N | 0.379 | 0.174 | None | gnomAD-4.0.0 | 3.10831E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.24698E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5622 | ambiguous | 0.4765 | ambiguous | -0.23 | Destabilizing | 0.927 | D | 0.473 | neutral | None | None | None | None | N |
| M/C | 0.8647 | likely_pathogenic | 0.8414 | pathogenic | -0.368 | Destabilizing | 0.999 | D | 0.475 | neutral | None | None | None | None | N |
| M/D | 0.8742 | likely_pathogenic | 0.8123 | pathogenic | 0.408 | Stabilizing | 0.997 | D | 0.541 | neutral | None | None | None | None | N |
| M/E | 0.6632 | likely_pathogenic | 0.5612 | ambiguous | 0.365 | Stabilizing | 0.997 | D | 0.509 | neutral | None | None | None | None | N |
| M/F | 0.487 | ambiguous | 0.4202 | ambiguous | -0.02 | Destabilizing | 0.939 | D | 0.444 | neutral | None | None | None | None | N |
| M/G | 0.749 | likely_pathogenic | 0.6741 | pathogenic | -0.376 | Destabilizing | 0.997 | D | 0.527 | neutral | None | None | None | None | N |
| M/H | 0.7843 | likely_pathogenic | 0.7194 | pathogenic | 0.364 | Stabilizing | 0.999 | D | 0.521 | neutral | None | None | None | None | N |
| M/I | 0.7177 | likely_pathogenic | 0.6361 | pathogenic | 0.06 | Stabilizing | 0.704 | D | 0.453 | neutral | N | 0.507134781 | None | None | N |
| M/K | 0.3573 | ambiguous | 0.3101 | benign | 0.464 | Stabilizing | 0.986 | D | 0.503 | neutral | N | 0.409233287 | None | None | N |
| M/L | 0.1547 | likely_benign | 0.1307 | benign | 0.06 | Stabilizing | 0.005 | N | 0.171 | neutral | N | 0.470627715 | None | None | N |
| M/N | 0.7072 | likely_pathogenic | 0.6284 | pathogenic | 0.549 | Stabilizing | 0.997 | D | 0.527 | neutral | None | None | None | None | N |
| M/P | 0.932 | likely_pathogenic | 0.9018 | pathogenic | -0.01 | Destabilizing | 0.997 | D | 0.521 | neutral | None | None | None | None | N |
| M/Q | 0.4536 | ambiguous | 0.3851 | ambiguous | 0.432 | Stabilizing | 0.997 | D | 0.45 | neutral | None | None | None | None | N |
| M/R | 0.3764 | ambiguous | 0.319 | benign | 0.872 | Stabilizing | 0.996 | D | 0.481 | neutral | N | 0.496290896 | None | None | N |
| M/S | 0.6497 | likely_pathogenic | 0.5713 | pathogenic | 0.126 | Stabilizing | 0.99 | D | 0.473 | neutral | None | None | None | None | N |
| M/T | 0.5446 | ambiguous | 0.4707 | ambiguous | 0.184 | Stabilizing | 0.959 | D | 0.453 | neutral | N | 0.493300321 | None | None | N |
| M/V | 0.2213 | likely_benign | 0.1879 | benign | -0.01 | Destabilizing | 0.704 | D | 0.379 | neutral | N | 0.504820361 | None | None | N |
| M/W | 0.7697 | likely_pathogenic | 0.7214 | pathogenic | -0.048 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | N |
| M/Y | 0.7639 | likely_pathogenic | 0.6921 | pathogenic | 0.145 | Stabilizing | 0.997 | D | 0.485 | 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.