Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26701 | 80326;80327;80328 | chr2:178566031;178566030;178566029 | chr2:179430758;179430757;179430756 |
| N2AB | 25060 | 75403;75404;75405 | chr2:178566031;178566030;178566029 | chr2:179430758;179430757;179430756 |
| N2A | 24133 | 72622;72623;72624 | chr2:178566031;178566030;178566029 | chr2:179430758;179430757;179430756 |
| N2B | 17636 | 53131;53132;53133 | chr2:178566031;178566030;178566029 | chr2:179430758;179430757;179430756 |
| Novex-1 | 17761 | 53506;53507;53508 | chr2:178566031;178566030;178566029 | chr2:179430758;179430757;179430756 |
| Novex-2 | 17828 | 53707;53708;53709 | chr2:178566031;178566030;178566029 | chr2:179430758;179430757;179430756 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs575784937  |
-1.759 | None | N | 0.154 | 0.145 | 0.0806252709748 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.61592E-04 | None | 0 | 0 | 0 |
| F/L | rs575784937 |
-1.759 | None | N | 0.154 | 0.145 | 0.0806252709748 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06782E-04 | 0 |
| F/L | rs575784937 |
-1.759 | None | N | 0.154 | 0.145 | 0.0806252709748 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| F/L | rs575784937 |
-1.759 | None | N | 0.154 | 0.145 | 0.0806252709748 | gnomAD-4.0.0 | 1.40948E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.20627E-04 | 5.68699E-05 |
| F/S | rs954218807 |
None | 0.003 | N | 0.377 | 0.109 | 0.299770980665 | 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 |
| F/S | rs954218807 |
None | 0.003 | N | 0.377 | 0.109 | 0.299770980665 | gnomAD-4.0.0 | 6.57324E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47033E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.1889 | likely_benign | 0.1539 | benign | -2.564 | Highly Destabilizing | 0.002 | N | 0.385 | neutral | None | None | None | None | N |
| F/C | 0.1501 | likely_benign | 0.148 | benign | -1.286 | Destabilizing | 0.196 | N | 0.59 | neutral | N | 0.437633861 | None | None | N |
| F/D | 0.6 | likely_pathogenic | 0.5473 | ambiguous | -1.699 | Destabilizing | 0.018 | N | 0.524 | neutral | None | None | None | None | N |
| F/E | 0.62 | likely_pathogenic | 0.5364 | ambiguous | -1.581 | Destabilizing | 0.018 | N | 0.44 | neutral | None | None | None | None | N |
| F/G | 0.4394 | ambiguous | 0.3841 | ambiguous | -2.929 | Highly Destabilizing | 0.018 | N | 0.404 | neutral | None | None | None | None | N |
| F/H | 0.2489 | likely_benign | 0.2198 | benign | -1.132 | Destabilizing | 0.138 | N | 0.556 | neutral | None | None | None | None | N |
| F/I | 0.0777 | likely_benign | 0.0658 | benign | -1.433 | Destabilizing | None | N | 0.191 | neutral | N | 0.384511452 | None | None | N |
| F/K | 0.5975 | likely_pathogenic | 0.538 | ambiguous | -1.509 | Destabilizing | 0.018 | N | 0.439 | neutral | None | None | None | None | N |
| F/L | 0.2257 | likely_benign | 0.1866 | benign | -1.433 | Destabilizing | None | N | 0.154 | neutral | N | 0.376006612 | None | None | N |
| F/M | 0.1183 | likely_benign | 0.1016 | benign | -1.03 | Destabilizing | 0.022 | N | 0.427 | neutral | None | None | None | None | N |
| F/N | 0.2328 | likely_benign | 0.1783 | benign | -1.617 | Destabilizing | 0.018 | N | 0.561 | neutral | None | None | None | None | N |
| F/P | 0.9346 | likely_pathogenic | 0.9257 | pathogenic | -1.809 | Destabilizing | 0.085 | N | 0.599 | neutral | None | None | None | None | N |
| F/Q | 0.3802 | ambiguous | 0.3296 | benign | -1.711 | Destabilizing | 0.085 | N | 0.605 | neutral | None | None | None | None | N |
| F/R | 0.5038 | ambiguous | 0.4452 | ambiguous | -0.793 | Destabilizing | 0.044 | N | 0.603 | neutral | None | None | None | None | N |
| F/S | 0.1344 | likely_benign | 0.1043 | benign | -2.4 | Highly Destabilizing | 0.003 | N | 0.377 | neutral | N | 0.329618174 | None | None | N |
| F/T | 0.1073 | likely_benign | 0.087 | benign | -2.193 | Highly Destabilizing | None | N | 0.281 | neutral | None | None | None | None | N |
| F/V | 0.0726 | likely_benign | 0.0639 | benign | -1.809 | Destabilizing | None | N | 0.207 | neutral | N | 0.348107935 | None | None | N |
| F/W | 0.2799 | likely_benign | 0.2803 | benign | -0.411 | Destabilizing | 0.245 | N | 0.455 | neutral | None | None | None | None | N |
| F/Y | 0.1102 | likely_benign | 0.1095 | benign | -0.692 | Destabilizing | None | N | 0.187 | neutral | N | 0.429918455 | 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.