Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19340 | 58243;58244;58245 | chr2:178594476;178594475;178594474 | chr2:179459203;179459202;179459201 |
| N2AB | 17699 | 53320;53321;53322 | chr2:178594476;178594475;178594474 | chr2:179459203;179459202;179459201 |
| N2A | 16772 | 50539;50540;50541 | chr2:178594476;178594475;178594474 | chr2:179459203;179459202;179459201 |
| N2B | 10275 | 31048;31049;31050 | chr2:178594476;178594475;178594474 | chr2:179459203;179459202;179459201 |
| Novex-1 | 10400 | 31423;31424;31425 | chr2:178594476;178594475;178594474 | chr2:179459203;179459202;179459201 |
| Novex-2 | 10467 | 31624;31625;31626 | chr2:178594476;178594475;178594474 | chr2:179459203;179459202;179459201 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/H | rs777213118  |
-0.369 | 0.976 | N | 0.662 | 0.43 | 0.817808388354 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.81E-06 | 0 |
| L/H | rs777213118 |
-0.369 | 0.976 | N | 0.662 | 0.43 | 0.817808388354 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/H | rs777213118 |
-0.369 | 0.976 | N | 0.662 | 0.43 | 0.817808388354 | gnomAD-4.0.0 | 1.11575E-05 | None | None | None | None | N | None | 1.33526E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44121E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1994 | likely_benign | 0.2136 | benign | -1.398 | Destabilizing | 0.25 | N | 0.575 | neutral | None | None | None | None | N |
| L/C | 0.4806 | ambiguous | 0.4976 | ambiguous | -0.852 | Destabilizing | 0.982 | D | 0.64 | neutral | None | None | None | None | N |
| L/D | 0.5684 | likely_pathogenic | 0.5705 | pathogenic | -0.612 | Destabilizing | 0.826 | D | 0.689 | prob.neutral | None | None | None | None | N |
| L/E | 0.312 | likely_benign | 0.3114 | benign | -0.607 | Destabilizing | 0.826 | D | 0.693 | prob.neutral | None | None | None | None | N |
| L/F | 0.1647 | likely_benign | 0.159 | benign | -0.905 | Destabilizing | 0.638 | D | 0.594 | neutral | N | 0.494161934 | None | None | N |
| L/G | 0.3815 | ambiguous | 0.3983 | ambiguous | -1.709 | Destabilizing | 0.7 | D | 0.685 | prob.neutral | None | None | None | None | N |
| L/H | 0.2208 | likely_benign | 0.2147 | benign | -0.792 | Destabilizing | 0.976 | D | 0.662 | neutral | N | 0.460164004 | None | None | N |
| L/I | 0.1028 | likely_benign | 0.099 | benign | -0.63 | Destabilizing | 0.201 | N | 0.472 | neutral | N | 0.46993828 | None | None | N |
| L/K | 0.173 | likely_benign | 0.1762 | benign | -0.893 | Destabilizing | 0.7 | D | 0.602 | neutral | None | None | None | None | N |
| L/M | 0.0915 | likely_benign | 0.1106 | benign | -0.558 | Destabilizing | 0.009 | N | 0.171 | neutral | None | None | None | None | N |
| L/N | 0.2567 | likely_benign | 0.272 | benign | -0.739 | Destabilizing | 0.826 | D | 0.689 | prob.neutral | None | None | None | None | N |
| L/P | 0.183 | likely_benign | 0.1704 | benign | -0.854 | Destabilizing | 0.916 | D | 0.686 | prob.neutral | N | 0.425878072 | None | None | N |
| L/Q | 0.1264 | likely_benign | 0.1272 | benign | -0.878 | Destabilizing | 0.7 | D | 0.67 | neutral | None | None | None | None | N |
| L/R | 0.1859 | likely_benign | 0.1785 | benign | -0.324 | Destabilizing | 0.638 | D | 0.677 | prob.neutral | N | 0.406484235 | None | None | N |
| L/S | 0.212 | likely_benign | 0.2227 | benign | -1.364 | Destabilizing | 0.7 | D | 0.586 | neutral | None | None | None | None | N |
| L/T | 0.1453 | likely_benign | 0.1548 | benign | -1.235 | Destabilizing | 0.7 | D | 0.636 | neutral | None | None | None | None | N |
| L/V | 0.0937 | likely_benign | 0.0974 | benign | -0.854 | Destabilizing | 0.094 | N | 0.507 | neutral | N | 0.441404885 | None | None | N |
| L/W | 0.3557 | ambiguous | 0.3173 | benign | -0.951 | Destabilizing | 0.982 | D | 0.674 | neutral | None | None | None | None | N |
| L/Y | 0.3248 | likely_benign | 0.342 | ambiguous | -0.731 | Destabilizing | 0.826 | D | 0.661 | 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.