Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6716 | 20371;20372;20373 | chr2:178727219;178727218;178727217 | chr2:179591946;179591945;179591944 |
| N2AB | 6399 | 19420;19421;19422 | chr2:178727219;178727218;178727217 | chr2:179591946;179591945;179591944 |
| N2A | 5472 | 16639;16640;16641 | chr2:178727219;178727218;178727217 | chr2:179591946;179591945;179591944 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/I | rs1157627734  |
-0.802 | 0.435 | N | 0.368 | 0.188 | 0.571589692201 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| M/I | rs1157627734 |
-0.802 | 0.435 | N | 0.368 | 0.188 | 0.571589692201 | gnomAD-4.0.0 | 4.10675E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39841E-06 | 0 | 0 |
| M/K | rs28626194 |
-0.737 | 0.788 | N | 0.425 | 0.492 | None | gnomAD-2.1.1 | 1.8411E-03 | None | None | None | None | I | None | 1.99752E-02 | 7.36669E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.57E-05 | 4.22416E-04 |
| M/K | rs28626194 |
-0.737 | 0.788 | N | 0.425 | 0.492 | None | gnomAD-3.1.2 | 5.79323E-03 | None | None | None | None | I | None | 2.04884E-02 | 1.37633E-03 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 2.07297E-04 | 2.39006E-03 |
| M/K | rs28626194 |
-0.737 | 0.788 | N | 0.425 | 0.492 | None | 1000 genomes | 4.39297E-03 | None | None | None | None | I | None | 1.51E-02 | 2.9E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| M/K | rs28626194 |
-0.737 | 0.788 | N | 0.425 | 0.492 | None | gnomAD-4.0.0 | 1.0544E-03 | None | None | None | None | I | None | 2.07761E-02 | 9.0054E-04 | None | 0 | 0 | None | 0 | 3.30469E-04 | 1.18701E-05 | 4.39416E-05 | 1.10467E-03 |
| M/R | rs28626194 |
-0.275 | 0.983 | N | 0.513 | 0.484 | 0.766828981107 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 1.29282E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/R | rs28626194 |
-0.275 | 0.983 | N | 0.513 | 0.484 | 0.766828981107 | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| M/R | rs28626194 |
-0.275 | 0.983 | N | 0.513 | 0.484 | 0.766828981107 | gnomAD-4.0.0 | 1.8596E-06 | None | None | None | None | I | None | 4.00032E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6341 | likely_pathogenic | 0.6732 | pathogenic | -1.823 | Destabilizing | 0.847 | D | 0.349 | neutral | None | None | None | None | I |
| M/C | 0.9143 | likely_pathogenic | 0.9242 | pathogenic | -1.185 | Destabilizing | 0.998 | D | 0.485 | neutral | None | None | None | None | I |
| M/D | 0.9459 | likely_pathogenic | 0.9542 | pathogenic | -0.455 | Destabilizing | 0.966 | D | 0.589 | neutral | None | None | None | None | I |
| M/E | 0.7312 | likely_pathogenic | 0.7478 | pathogenic | -0.4 | Destabilizing | 0.764 | D | 0.503 | neutral | None | None | None | None | I |
| M/F | 0.3588 | ambiguous | 0.4319 | ambiguous | -0.75 | Destabilizing | 0.814 | D | 0.457 | neutral | None | None | None | None | I |
| M/G | 0.8327 | likely_pathogenic | 0.8566 | pathogenic | -2.165 | Highly Destabilizing | 0.964 | D | 0.553 | neutral | None | None | None | None | I |
| M/H | 0.7404 | likely_pathogenic | 0.785 | pathogenic | -1.231 | Destabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | I |
| M/I | 0.496 | ambiguous | 0.5421 | ambiguous | -0.927 | Destabilizing | 0.435 | N | 0.368 | neutral | N | 0.456249412 | None | None | I |
| M/K | 0.3916 | ambiguous | 0.5188 | ambiguous | -0.565 | Destabilizing | 0.788 | D | 0.425 | neutral | N | 0.507559701 | None | None | I |
| M/L | 0.2027 | likely_benign | 0.2295 | benign | -0.927 | Destabilizing | 0.005 | N | 0.079 | neutral | N | 0.484668164 | None | None | I |
| M/N | 0.7533 | likely_pathogenic | 0.7705 | pathogenic | -0.476 | Destabilizing | 0.966 | D | 0.549 | neutral | None | None | None | None | I |
| M/P | 0.8955 | likely_pathogenic | 0.921 | pathogenic | -1.199 | Destabilizing | 0.983 | D | 0.552 | neutral | None | None | None | None | I |
| M/Q | 0.4045 | ambiguous | 0.4094 | ambiguous | -0.496 | Destabilizing | 0.987 | D | 0.464 | neutral | None | None | None | None | I |
| M/R | 0.4253 | ambiguous | 0.4672 | ambiguous | -0.16 | Destabilizing | 0.983 | D | 0.513 | neutral | N | 0.496456885 | None | None | I |
| M/S | 0.6624 | likely_pathogenic | 0.6846 | pathogenic | -1.119 | Destabilizing | 0.847 | D | 0.419 | neutral | None | None | None | None | I |
| M/T | 0.4341 | ambiguous | 0.453 | ambiguous | -0.943 | Destabilizing | 0.033 | N | 0.205 | neutral | N | 0.514588427 | None | None | I |
| M/V | 0.1873 | likely_benign | 0.2051 | benign | -1.199 | Destabilizing | 0.633 | D | 0.279 | neutral | N | 0.504981935 | None | None | I |
| M/W | 0.7511 | likely_pathogenic | 0.8167 | pathogenic | -0.704 | Destabilizing | 1.0 | D | 0.487 | neutral | None | None | None | None | I |
| M/Y | 0.6839 | likely_pathogenic | 0.741 | pathogenic | -0.735 | Destabilizing | 0.997 | D | 0.493 | neutral | None | None | None | None | I |
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.