Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2941 | 9046;9047;9048 | chr2:178769760;178769759;178769758 | chr2:179634487;179634486;179634485 |
| N2AB | 2941 | 9046;9047;9048 | chr2:178769760;178769759;178769758 | chr2:179634487;179634486;179634485 |
| N2A | 2941 | 9046;9047;9048 | chr2:178769760;178769759;178769758 | chr2:179634487;179634486;179634485 |
| N2B | 2895 | 8908;8909;8910 | chr2:178769760;178769759;178769758 | chr2:179634487;179634486;179634485 |
| Novex-1 | 2895 | 8908;8909;8910 | chr2:178769760;178769759;178769758 | chr2:179634487;179634486;179634485 |
| Novex-2 | 2895 | 8908;8909;8910 | chr2:178769760;178769759;178769758 | chr2:179634487;179634486;179634485 |
| Novex-3 | 2941 | 9046;9047;9048 | chr2:178769760;178769759;178769758 | chr2:179634487;179634486;179634485 |
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 | 0.122 | 0.242 | 0.526842377483 | gnomAD-4.0.0 | 1.59049E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85656E-06 | 0 | 0 |
| M/T | rs766700696  |
-0.546 | 0.801 | N | 0.315 | 0.47 | 0.78743447906 | gnomAD-2.1.1 | 7.09E-06 | None | None | None | None | N | None | 4.01E-05 | 2.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs766700696 |
-0.546 | 0.801 | N | 0.315 | 0.47 | 0.78743447906 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs766700696 |
-0.546 | 0.801 | N | 0.315 | 0.47 | 0.78743447906 | gnomAD-4.0.0 | 5.12315E-06 | None | None | None | None | N | None | 3.38535E-05 | 3.38983E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs1344696996 |
-0.722 | 0.022 | N | 0.112 | 0.279 | 0.431712495121 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.63345E-04 |
| M/V | rs1344696996 |
-0.722 | 0.022 | N | 0.112 | 0.279 | 0.431712495121 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| M/V | rs1344696996 |
-0.722 | 0.022 | N | 0.112 | 0.279 | 0.431712495121 | gnomAD-4.0.0 | 6.40323E-06 | None | None | None | None | N | None | 1.69147E-05 | 0 | None | 0 | 0 | None | 0 | 2.24115E-04 | 2.39184E-06 | 0 | 5.68376E-05 |
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 | 0.6471 | likely_pathogenic | 0.5896 | pathogenic | -1.629 | Destabilizing | 0.688 | D | 0.307 | neutral | None | None | None | None | N |
| M/C | 0.7972 | likely_pathogenic | 0.8435 | pathogenic | -1.404 | Destabilizing | 0.998 | D | 0.355 | neutral | None | None | None | None | N |
| M/D | 0.9318 | likely_pathogenic | 0.9124 | pathogenic | -0.918 | Destabilizing | 0.991 | D | 0.433 | neutral | None | None | None | None | N |
| M/E | 0.6852 | likely_pathogenic | 0.6483 | pathogenic | -0.899 | Destabilizing | 0.971 | D | 0.401 | neutral | None | None | None | None | N |
| M/F | 0.4952 | ambiguous | 0.5001 | ambiguous | -0.812 | Destabilizing | 0.842 | D | 0.314 | neutral | None | None | None | None | N |
| M/G | 0.8083 | likely_pathogenic | 0.7757 | pathogenic | -1.931 | Destabilizing | 0.971 | D | 0.421 | neutral | None | None | None | None | N |
| M/H | 0.6263 | likely_pathogenic | 0.6373 | pathogenic | -1.096 | Destabilizing | 0.998 | D | 0.389 | neutral | None | None | None | None | N |
| M/I | 0.492 | ambiguous | 0.4821 | ambiguous | -0.855 | Destabilizing | 0.454 | N | 0.236 | neutral | N | 0.4869721 | None | None | N |
| M/K | 0.3328 | likely_benign | 0.3243 | benign | -0.544 | Destabilizing | 0.891 | D | 0.377 | neutral | N | 0.451301717 | None | None | N |
| M/L | 0.1762 | likely_benign | 0.1555 | benign | -0.855 | Destabilizing | 0.005 | N | 0.122 | neutral | N | 0.447516858 | None | None | N |
| M/N | 0.665 | likely_pathogenic | 0.609 | pathogenic | -0.43 | Destabilizing | 0.991 | D | 0.405 | neutral | None | None | None | None | N |
| M/P | 0.9601 | likely_pathogenic | 0.9235 | pathogenic | -1.086 | Destabilizing | 0.991 | D | 0.4 | neutral | None | None | None | None | N |
| M/Q | 0.3584 | ambiguous | 0.3491 | ambiguous | -0.559 | Destabilizing | 0.991 | D | 0.324 | neutral | None | None | None | None | N |
| M/R | 0.3254 | likely_benign | 0.3208 | benign | -0.093 | Destabilizing | 0.966 | D | 0.378 | neutral | N | 0.450860841 | None | None | N |
| M/S | 0.6304 | likely_pathogenic | 0.5788 | pathogenic | -0.994 | Destabilizing | 0.915 | D | 0.315 | neutral | None | None | None | None | N |
| M/T | 0.3436 | ambiguous | 0.2988 | benign | -0.867 | Destabilizing | 0.801 | D | 0.315 | neutral | N | 0.487633665 | None | None | N |
| M/V | 0.1551 | likely_benign | 0.1458 | benign | -1.086 | Destabilizing | 0.022 | N | 0.112 | neutral | N | 0.447871277 | None | None | N |
| M/W | 0.7331 | likely_pathogenic | 0.766 | pathogenic | -0.773 | Destabilizing | 0.998 | D | 0.389 | neutral | None | None | None | None | N |
| M/Y | 0.7131 | likely_pathogenic | 0.7337 | pathogenic | -0.74 | Destabilizing | 0.974 | D | 0.384 | 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.