Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26132 | 78619;78620;78621 | chr2:178567738;178567737;178567736 | chr2:179432465;179432464;179432463 |
| N2AB | 24491 | 73696;73697;73698 | chr2:178567738;178567737;178567736 | chr2:179432465;179432464;179432463 |
| N2A | 23564 | 70915;70916;70917 | chr2:178567738;178567737;178567736 | chr2:179432465;179432464;179432463 |
| N2B | 17067 | 51424;51425;51426 | chr2:178567738;178567737;178567736 | chr2:179432465;179432464;179432463 |
| Novex-1 | 17192 | 51799;51800;51801 | chr2:178567738;178567737;178567736 | chr2:179432465;179432464;179432463 |
| Novex-2 | 17259 | 52000;52001;52002 | chr2:178567738;178567737;178567736 | chr2:179432465;179432464;179432463 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs757198030  |
-0.261 | 0.117 | N | 0.296 | 0.188 | 0.256793551483 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 1.29249E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| D/N | rs757198030 |
-0.261 | 0.117 | N | 0.296 | 0.188 | 0.256793551483 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs757198030 |
-0.261 | 0.117 | N | 0.296 | 0.188 | 0.256793551483 | gnomAD-4.0.0 | 5.58078E-06 | None | None | None | None | N | None | 2.67094E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.9369E-06 | 0 | 0 |
| D/Y | rs757198030 |
None | 0.741 | N | 0.474 | 0.509 | 0.625503179482 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66389E-04 |
| D/Y | rs757198030 |
None | 0.741 | N | 0.474 | 0.509 | 0.625503179482 | gnomAD-4.0.0 | 6.84647E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65766E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1268 | likely_benign | 0.1112 | benign | 0.058 | Stabilizing | 0.062 | N | 0.332 | neutral | N | 0.487697322 | None | None | N |
| D/C | 0.5655 | likely_pathogenic | 0.5406 | ambiguous | -0.152 | Destabilizing | 0.935 | D | 0.519 | neutral | None | None | None | None | N |
| D/E | 0.0698 | likely_benign | 0.0723 | benign | -0.357 | Destabilizing | None | N | 0.147 | neutral | N | 0.428494303 | None | None | N |
| D/F | 0.5769 | likely_pathogenic | 0.527 | ambiguous | -0.074 | Destabilizing | 0.791 | D | 0.478 | neutral | None | None | None | None | N |
| D/G | 0.1388 | likely_benign | 0.1309 | benign | -0.043 | Destabilizing | 0.117 | N | 0.29 | neutral | N | 0.450504371 | None | None | N |
| D/H | 0.2905 | likely_benign | 0.2591 | benign | 0.543 | Stabilizing | 0.484 | N | 0.337 | neutral | N | 0.470496638 | None | None | N |
| D/I | 0.3575 | ambiguous | 0.3157 | benign | 0.254 | Stabilizing | 0.555 | D | 0.472 | neutral | None | None | None | None | N |
| D/K | 0.284 | likely_benign | 0.2658 | benign | 0.41 | Stabilizing | 0.081 | N | 0.296 | neutral | None | None | None | None | N |
| D/L | 0.326 | likely_benign | 0.2804 | benign | 0.254 | Stabilizing | 0.38 | N | 0.438 | neutral | None | None | None | None | N |
| D/M | 0.4872 | ambiguous | 0.4476 | ambiguous | 0.03 | Stabilizing | 0.935 | D | 0.475 | neutral | None | None | None | None | N |
| D/N | 0.0924 | likely_benign | 0.0918 | benign | 0.213 | Stabilizing | 0.117 | N | 0.296 | neutral | N | 0.470284997 | None | None | N |
| D/P | 0.7146 | likely_pathogenic | 0.6743 | pathogenic | 0.207 | Stabilizing | 0.555 | D | 0.322 | neutral | None | None | None | None | N |
| D/Q | 0.2227 | likely_benign | 0.2106 | benign | 0.201 | Stabilizing | 0.081 | N | 0.249 | neutral | None | None | None | None | N |
| D/R | 0.3823 | ambiguous | 0.3476 | ambiguous | 0.634 | Stabilizing | 0.235 | N | 0.397 | neutral | None | None | None | None | N |
| D/S | 0.1047 | likely_benign | 0.0996 | benign | 0.115 | Stabilizing | 0.081 | N | 0.3 | neutral | None | None | None | None | N |
| D/T | 0.1905 | likely_benign | 0.1755 | benign | 0.198 | Stabilizing | 0.149 | N | 0.321 | neutral | None | None | None | None | N |
| D/V | 0.2104 | likely_benign | 0.1842 | benign | 0.207 | Stabilizing | 0.317 | N | 0.437 | neutral | N | 0.474219621 | None | None | N |
| D/W | 0.8615 | likely_pathogenic | 0.8388 | pathogenic | -0.054 | Destabilizing | 0.935 | D | 0.564 | neutral | None | None | None | None | N |
| D/Y | 0.2806 | likely_benign | 0.2529 | benign | 0.147 | Stabilizing | 0.741 | D | 0.474 | neutral | N | 0.486082906 | 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.