Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14024 | 42295;42296;42297 | chr2:178634804;178634803;178634802 | chr2:179499531;179499530;179499529 |
| N2AB | 12383 | 37372;37373;37374 | chr2:178634804;178634803;178634802 | chr2:179499531;179499530;179499529 |
| N2A | 11456 | 34591;34592;34593 | chr2:178634804;178634803;178634802 | chr2:179499531;179499530;179499529 |
| N2B | 4959 | 15100;15101;15102 | chr2:178634804;178634803;178634802 | chr2:179499531;179499530;179499529 |
| Novex-1 | 5084 | 15475;15476;15477 | chr2:178634804;178634803;178634802 | chr2:179499531;179499530;179499529 |
| Novex-2 | 5151 | 15676;15677;15678 | chr2:178634804;178634803;178634802 | chr2:179499531;179499530;179499529 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/P | None | None | None | N | None | 0.303 | None | gnomAD-4.0.0 | 3.42318E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49898E-06 | 0 | 0 |
| H/Q | rs1276854895  |
-0.021 | None | N | None | 0.083 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| H/Q | rs1276854895 |
-0.021 | None | N | None | 0.083 | None | gnomAD-4.0.0 | 1.59357E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43633E-05 | 0 |
| H/R | rs2288563 |
-0.49 | None | N | 0.043 | 0.128 | None | gnomAD-2.1.1 | 2.85073E-02 | None | None | None | None | N | None | 4.9636E-03 | 3.32537E-02 | None | 1.47144E-02 | 1.01869E-01 | None | 6.3799E-03 | None | 4.81085E-02 | 2.3141E-02 | 2.74339E-02 |
| H/R | rs2288563 |
-0.49 | None | N | 0.043 | 0.128 | None | gnomAD-3.1.2 | 2.15088E-02 | None | None | None | None | N | None | 4.60818E-03 | 2.32009E-02 | 3.07018E-02 | 1.90202E-02 | 9.65557E-02 | None | 4.51892E-02 | 6.32911E-03 | 2.30561E-02 | 8.06785E-03 | 2.15517E-02 |
| H/R | rs2288563 |
-0.49 | None | N | 0.043 | 0.128 | None | 1000 genomes | 3.05511E-02 | None | None | None | None | N | None | 8E-04 | 2.74E-02 | None | None | 9.92E-02 | 2.68E-02 | None | None | None | 6.1E-03 | None |
| H/R | rs2288563 |
-0.49 | None | N | 0.043 | 0.128 | None | gnomAD-4.0.0 | 2.36264E-02 | None | None | None | None | N | None | 4.37602E-03 | 2.95513E-02 | None | 1.48749E-02 | 9.58164E-02 | None | 4.83407E-02 | 9.91408E-03 | 2.20434E-02 | 6.97362E-03 | 2.3451E-02 |
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 | 0.8973 | likely_pathogenic | 0.8687 | pathogenic | -0.402 | Destabilizing | None | None | None | None | None | None | None | None | N |
| H/C | 0.721 | likely_pathogenic | 0.6639 | pathogenic | 0.251 | Stabilizing | None | None | None | None | None | None | None | None | N |
| H/D | 0.851 | likely_pathogenic | 0.8368 | pathogenic | -0.026 | Destabilizing | None | None | None | None | N | 0.444878128 | None | None | N |
| H/E | 0.8427 | likely_pathogenic | 0.8073 | pathogenic | 0.009 | Stabilizing | None | None | None | None | None | None | None | None | N |
| H/F | 0.7892 | likely_pathogenic | 0.6898 | pathogenic | 0.027 | Stabilizing | None | None | None | None | None | None | None | None | N |
| H/G | 0.8721 | likely_pathogenic | 0.8364 | pathogenic | -0.694 | Destabilizing | None | None | None | None | None | None | None | None | N |
| H/I | 0.9242 | likely_pathogenic | 0.8869 | pathogenic | 0.359 | Stabilizing | None | None | None | None | None | None | None | None | N |
| H/K | 0.6104 | likely_pathogenic | 0.5642 | pathogenic | -0.268 | Destabilizing | None | None | None | None | None | None | None | None | N |
| H/L | 0.5812 | likely_pathogenic | 0.4754 | ambiguous | 0.359 | Stabilizing | None | None | None | None | N | 0.422705095 | None | None | N |
| H/M | 0.9181 | likely_pathogenic | 0.8779 | pathogenic | 0.347 | Stabilizing | None | None | None | None | None | None | None | None | N |
| H/N | 0.4563 | ambiguous | 0.4031 | ambiguous | -0.038 | Destabilizing | None | None | None | None | N | 0.43203766 | None | None | N |
| H/P | 0.8128 | likely_pathogenic | 0.8434 | pathogenic | 0.129 | Stabilizing | None | None | None | None | N | 0.425817864 | None | None | N |
| H/Q | 0.5966 | likely_pathogenic | 0.5293 | ambiguous | 0.031 | Stabilizing | None | None | None | None | N | 0.426565587 | None | None | N |
| H/R | 0.3913 | ambiguous | 0.1886 | benign | -0.537 | Destabilizing | None | N | 0.043 | neutral | N | 0.431633 | None | None | N |
| H/S | 0.7706 | likely_pathogenic | 0.7265 | pathogenic | -0.175 | Destabilizing | None | None | None | None | None | None | None | None | N |
| H/T | 0.8399 | likely_pathogenic | 0.8088 | pathogenic | -0.05 | Destabilizing | None | None | None | None | None | None | None | None | N |
| H/V | 0.8853 | likely_pathogenic | 0.8431 | pathogenic | 0.129 | Stabilizing | None | None | None | None | None | None | None | None | N |
| H/W | 0.7829 | likely_pathogenic | 0.6959 | pathogenic | 0.11 | Stabilizing | None | None | None | None | None | None | None | None | N |
| H/Y | 0.3797 | ambiguous | 0.2778 | benign | 0.481 | Stabilizing | None | None | None | None | N | 0.434476456 | 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.