Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25601 | 77026;77027;77028 | chr2:178569331;178569330;178569329 | chr2:179434058;179434057;179434056 |
| N2AB | 23960 | 72103;72104;72105 | chr2:178569331;178569330;178569329 | chr2:179434058;179434057;179434056 |
| N2A | 23033 | 69322;69323;69324 | chr2:178569331;178569330;178569329 | chr2:179434058;179434057;179434056 |
| N2B | 16536 | 49831;49832;49833 | chr2:178569331;178569330;178569329 | chr2:179434058;179434057;179434056 |
| Novex-1 | 16661 | 50206;50207;50208 | chr2:178569331;178569330;178569329 | chr2:179434058;179434057;179434056 |
| Novex-2 | 16728 | 50407;50408;50409 | chr2:178569331;178569330;178569329 | chr2:179434058;179434057;179434056 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | rs374913031  |
-0.475 | 0.998 | N | 0.577 | 0.373 | 0.268211541103 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| T/K | rs374913031 |
-0.475 | 0.998 | N | 0.577 | 0.373 | 0.268211541103 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/K | rs374913031 |
-0.475 | 0.998 | N | 0.577 | 0.373 | 0.268211541103 | gnomAD-4.0.0 | 3.71946E-06 | None | None | None | None | I | None | 1.33547E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47823E-07 | 3.29757E-05 | 1.60149E-05 |
| T/M | rs374913031 |
-0.18 | 1.0 | N | 0.55 | 0.375 | None | gnomAD-2.1.1 | 5.24E-05 | None | None | None | None | I | None | 2.58632E-04 | 0 | None | 0 | 0 | None | 2.62072E-04 | None | 0 | 8.91E-06 | 0 |
| T/M | rs374913031 |
-0.18 | 1.0 | N | 0.55 | 0.375 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 7.24E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.13907E-04 | 0 |
| T/M | rs374913031 |
-0.18 | 1.0 | N | 0.55 | 0.375 | None | gnomAD-4.0.0 | 2.0457E-05 | None | None | None | None | I | None | 8.01282E-05 | 3.33667E-05 | None | 0 | 0 | None | 0 | 0 | 5.08694E-06 | 1.97854E-04 | 1.60149E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2172 | likely_benign | 0.2335 | benign | -0.943 | Destabilizing | 0.475 | N | 0.363 | neutral | N | 0.509250738 | None | None | I |
| T/C | 0.6861 | likely_pathogenic | 0.7258 | pathogenic | -0.573 | Destabilizing | 1.0 | D | 0.577 | neutral | None | None | None | None | I |
| T/D | 0.9123 | likely_pathogenic | 0.9236 | pathogenic | -0.092 | Destabilizing | 0.984 | D | 0.585 | neutral | None | None | None | None | I |
| T/E | 0.8537 | likely_pathogenic | 0.8638 | pathogenic | -0.141 | Destabilizing | 0.995 | D | 0.579 | neutral | None | None | None | None | I |
| T/F | 0.7776 | likely_pathogenic | 0.8204 | pathogenic | -1.334 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| T/G | 0.6072 | likely_pathogenic | 0.6043 | pathogenic | -1.104 | Destabilizing | 0.993 | D | 0.563 | neutral | None | None | None | None | I |
| T/H | 0.7051 | likely_pathogenic | 0.7467 | pathogenic | -1.468 | Destabilizing | 1.0 | D | 0.722 | deleterious | None | None | None | None | I |
| T/I | 0.5678 | likely_pathogenic | 0.6175 | pathogenic | -0.617 | Destabilizing | 0.998 | D | 0.585 | neutral | None | None | None | None | I |
| T/K | 0.6875 | likely_pathogenic | 0.7165 | pathogenic | -0.589 | Destabilizing | 0.998 | D | 0.577 | neutral | N | 0.440756232 | None | None | I |
| T/L | 0.3835 | ambiguous | 0.4246 | ambiguous | -0.617 | Destabilizing | 0.994 | D | 0.612 | neutral | None | None | None | None | I |
| T/M | 0.2562 | likely_benign | 0.2781 | benign | -0.154 | Destabilizing | 1.0 | D | 0.55 | neutral | N | 0.480606771 | None | None | I |
| T/N | 0.4504 | ambiguous | 0.4837 | ambiguous | -0.41 | Destabilizing | 0.984 | D | 0.588 | neutral | None | None | None | None | I |
| T/P | 0.4315 | ambiguous | 0.478 | ambiguous | -0.699 | Destabilizing | 0.99 | D | 0.581 | neutral | N | 0.483832218 | None | None | I |
| T/Q | 0.6818 | likely_pathogenic | 0.7085 | pathogenic | -0.73 | Destabilizing | 0.996 | D | 0.543 | neutral | None | None | None | None | I |
| T/R | 0.6754 | likely_pathogenic | 0.7288 | pathogenic | -0.304 | Destabilizing | 1.0 | D | 0.591 | neutral | N | 0.467134757 | None | None | I |
| T/S | 0.1374 | likely_benign | 0.1599 | benign | -0.725 | Destabilizing | 0.146 | N | 0.132 | neutral | N | 0.45289881 | None | None | I |
| T/V | 0.3887 | ambiguous | 0.4427 | ambiguous | -0.699 | Destabilizing | 0.992 | D | 0.599 | neutral | None | None | None | None | I |
| T/W | 0.9559 | likely_pathogenic | 0.9681 | pathogenic | -1.194 | Destabilizing | 1.0 | D | 0.706 | prob.delet. | None | None | None | None | I |
| T/Y | 0.7553 | likely_pathogenic | 0.7877 | pathogenic | -0.966 | Destabilizing | 1.0 | D | 0.751 | deleterious | 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.