Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23208 | 69847;69848;69849 | chr2:178576622;178576621;178576620 | chr2:179441349;179441348;179441347 |
| N2AB | 21567 | 64924;64925;64926 | chr2:178576622;178576621;178576620 | chr2:179441349;179441348;179441347 |
| N2A | 20640 | 62143;62144;62145 | chr2:178576622;178576621;178576620 | chr2:179441349;179441348;179441347 |
| N2B | 14143 | 42652;42653;42654 | chr2:178576622;178576621;178576620 | chr2:179441349;179441348;179441347 |
| Novex-1 | 14268 | 43027;43028;43029 | chr2:178576622;178576621;178576620 | chr2:179441349;179441348;179441347 |
| Novex-2 | 14335 | 43228;43229;43230 | chr2:178576622;178576621;178576620 | chr2:179441349;179441348;179441347 |
| 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/G | rs1559463266  |
None | 0.012 | N | 0.283 | 0.065 | 0.159798565429 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/G | rs1559463266 |
None | 0.012 | N | 0.283 | 0.065 | 0.159798565429 | gnomAD-4.0.0 | 2.7371E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79912E-06 | 2.31889E-05 | 0 |
| S/N | None | None | None | N | 0.066 | 0.142 | 0.112648838833 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/R | None | None | 0.055 | N | 0.445 | 0.095 | 0.151104730317 | gnomAD-4.0.0 | 6.8427E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99551E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0968 | likely_benign | 0.0916 | benign | -0.793 | Destabilizing | 0.007 | N | 0.261 | neutral | None | None | None | None | N |
| S/C | 0.0702 | likely_benign | 0.0694 | benign | -0.521 | Destabilizing | None | N | 0.227 | neutral | N | 0.469170276 | None | None | N |
| S/D | 0.4111 | ambiguous | 0.4056 | ambiguous | -0.362 | Destabilizing | 0.016 | N | 0.241 | neutral | None | None | None | None | N |
| S/E | 0.5454 | ambiguous | 0.5387 | ambiguous | -0.341 | Destabilizing | 0.016 | N | 0.248 | neutral | None | None | None | None | N |
| S/F | 0.2311 | likely_benign | 0.2185 | benign | -0.81 | Destabilizing | 0.356 | N | 0.479 | neutral | None | None | None | None | N |
| S/G | 0.0883 | likely_benign | 0.0871 | benign | -1.071 | Destabilizing | 0.012 | N | 0.283 | neutral | N | 0.457683846 | None | None | N |
| S/H | 0.2295 | likely_benign | 0.2283 | benign | -1.433 | Destabilizing | 0.214 | N | 0.388 | neutral | None | None | None | None | N |
| S/I | 0.1354 | likely_benign | 0.1418 | benign | -0.15 | Destabilizing | None | N | 0.185 | neutral | N | 0.44744821 | None | None | N |
| S/K | 0.5854 | likely_pathogenic | 0.5857 | pathogenic | -0.736 | Destabilizing | 0.016 | N | 0.25 | neutral | None | None | None | None | N |
| S/L | 0.1359 | likely_benign | 0.1363 | benign | -0.15 | Destabilizing | 0.007 | N | 0.264 | neutral | None | None | None | None | N |
| S/M | 0.1705 | likely_benign | 0.1696 | benign | 0.074 | Stabilizing | 0.356 | N | 0.393 | neutral | None | None | None | None | N |
| S/N | 0.0777 | likely_benign | 0.0777 | benign | -0.741 | Destabilizing | None | N | 0.066 | neutral | N | 0.421339044 | None | None | N |
| S/P | 0.8746 | likely_pathogenic | 0.8893 | pathogenic | -0.33 | Destabilizing | 0.136 | N | 0.445 | neutral | None | None | None | None | N |
| S/Q | 0.4019 | ambiguous | 0.3872 | ambiguous | -0.86 | Destabilizing | 0.072 | N | 0.378 | neutral | None | None | None | None | N |
| S/R | 0.5267 | ambiguous | 0.5309 | ambiguous | -0.62 | Destabilizing | 0.055 | N | 0.445 | neutral | N | 0.427955585 | None | None | N |
| S/T | 0.0956 | likely_benign | 0.0947 | benign | -0.75 | Destabilizing | 0.012 | N | 0.287 | neutral | N | 0.389546339 | None | None | N |
| S/V | 0.1413 | likely_benign | 0.139 | benign | -0.33 | Destabilizing | None | N | 0.137 | neutral | None | None | None | None | N |
| S/W | 0.4416 | ambiguous | 0.4431 | ambiguous | -0.792 | Destabilizing | 0.864 | D | 0.473 | neutral | None | None | None | None | N |
| S/Y | 0.1854 | likely_benign | 0.1823 | benign | -0.535 | Destabilizing | 0.628 | D | 0.479 | 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.