Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19341 | 58246;58247;58248 | chr2:178594473;178594472;178594471 | chr2:179459200;179459199;179459198 |
| N2AB | 17700 | 53323;53324;53325 | chr2:178594473;178594472;178594471 | chr2:179459200;179459199;179459198 |
| N2A | 16773 | 50542;50543;50544 | chr2:178594473;178594472;178594471 | chr2:179459200;179459199;179459198 |
| N2B | 10276 | 31051;31052;31053 | chr2:178594473;178594472;178594471 | chr2:179459200;179459199;179459198 |
| Novex-1 | 10401 | 31426;31427;31428 | chr2:178594473;178594472;178594471 | chr2:179459200;179459199;179459198 |
| Novex-2 | 10468 | 31627;31628;31629 | chr2:178594473;178594472;178594471 | chr2:179459200;179459199;179459198 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs536645864  |
-0.141 | None | N | 0.083 | 0.114 | None | gnomAD-2.1.1 | 7.64E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 5.88543E-04 | None | 0 | 8.88E-06 | 0 |
| S/N | rs536645864 |
-0.141 | None | N | 0.083 | 0.114 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07125E-04 | 0 |
| S/N | rs536645864 |
-0.141 | None | N | 0.083 | 0.114 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| S/N | rs536645864 |
-0.141 | None | N | 0.083 | 0.114 | None | gnomAD-4.0.0 | 4.71078E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.65235E-04 | 1.01735E-05 | 6.15101E-04 | 1.12061E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0938 | likely_benign | 0.0909 | benign | -0.63 | Destabilizing | 0.025 | N | 0.231 | neutral | None | None | None | None | N |
| S/C | 0.1354 | likely_benign | 0.1278 | benign | -0.478 | Destabilizing | 0.946 | D | 0.332 | neutral | N | 0.493508573 | None | None | N |
| S/D | 0.1929 | likely_benign | 0.1731 | benign | -0.056 | Destabilizing | None | N | 0.07 | neutral | None | None | None | None | N |
| S/E | 0.3032 | likely_benign | 0.2867 | benign | 0.038 | Stabilizing | 0.002 | N | 0.094 | neutral | None | None | None | None | N |
| S/F | 0.2962 | likely_benign | 0.2874 | benign | -0.973 | Destabilizing | 0.859 | D | 0.432 | neutral | None | None | None | None | N |
| S/G | 0.0899 | likely_benign | 0.0794 | benign | -0.877 | Destabilizing | None | N | 0.07 | neutral | N | 0.436076423 | None | None | N |
| S/H | 0.2788 | likely_benign | 0.2837 | benign | -0.871 | Destabilizing | 0.497 | N | 0.378 | neutral | None | None | None | None | N |
| S/I | 0.1996 | likely_benign | 0.1864 | benign | -0.049 | Destabilizing | 0.602 | D | 0.5 | neutral | N | 0.458875925 | None | None | N |
| S/K | 0.5438 | ambiguous | 0.5284 | ambiguous | 0.021 | Stabilizing | 0.055 | N | 0.251 | neutral | None | None | None | None | N |
| S/L | 0.1346 | likely_benign | 0.1319 | benign | -0.049 | Destabilizing | 0.22 | N | 0.425 | neutral | None | None | None | None | N |
| S/M | 0.2053 | likely_benign | 0.2086 | benign | -0.32 | Destabilizing | 0.859 | D | 0.352 | neutral | None | None | None | None | N |
| S/N | 0.0788 | likely_benign | 0.0858 | benign | -0.362 | Destabilizing | None | N | 0.083 | neutral | N | 0.457489058 | None | None | N |
| S/P | 0.3687 | ambiguous | 0.3319 | benign | -0.214 | Destabilizing | 0.364 | N | 0.381 | neutral | None | None | None | None | N |
| S/Q | 0.3456 | ambiguous | 0.35 | ambiguous | -0.268 | Destabilizing | 0.22 | N | 0.236 | neutral | None | None | None | None | N |
| S/R | 0.561 | ambiguous | 0.5351 | ambiguous | 0.007 | Stabilizing | 0.175 | N | 0.353 | neutral | N | 0.458009133 | None | None | N |
| S/T | 0.0792 | likely_benign | 0.0807 | benign | -0.356 | Destabilizing | 0.081 | N | 0.274 | neutral | N | 0.39110935 | None | None | N |
| S/V | 0.1903 | likely_benign | 0.1863 | benign | -0.214 | Destabilizing | 0.364 | N | 0.419 | neutral | None | None | None | None | N |
| S/W | 0.486 | ambiguous | 0.4755 | ambiguous | -1.099 | Destabilizing | 0.958 | D | 0.449 | neutral | None | None | None | None | N |
| S/Y | 0.2479 | likely_benign | 0.254 | benign | -0.682 | Destabilizing | 0.859 | D | 0.432 | 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.