Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19882 | 59869;59870;59871 | chr2:178592260;178592259;178592258 | chr2:179456987;179456986;179456985 |
| N2AB | 18241 | 54946;54947;54948 | chr2:178592260;178592259;178592258 | chr2:179456987;179456986;179456985 |
| N2A | 17314 | 52165;52166;52167 | chr2:178592260;178592259;178592258 | chr2:179456987;179456986;179456985 |
| N2B | 10817 | 32674;32675;32676 | chr2:178592260;178592259;178592258 | chr2:179456987;179456986;179456985 |
| Novex-1 | 10942 | 33049;33050;33051 | chr2:178592260;178592259;178592258 | chr2:179456987;179456986;179456985 |
| Novex-2 | 11009 | 33250;33251;33252 | chr2:178592260;178592259;178592258 | chr2:179456987;179456986;179456985 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/T | rs1309373929  |
-0.247 | 0.98 | N | 0.548 | 0.295 | 0.418344901717 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.1E-06 | 0 |
| R/T | rs1309373929 |
-0.247 | 0.98 | N | 0.548 | 0.295 | 0.418344901717 | 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 |
| R/T | rs1309373929 |
-0.247 | 0.98 | N | 0.548 | 0.295 | 0.418344901717 | gnomAD-4.0.0 | 2.56972E-06 | None | None | None | None | N | None | 1.69405E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39771E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.261 | likely_benign | 0.2792 | benign | -0.559 | Destabilizing | 0.931 | D | 0.513 | neutral | None | None | None | None | N |
| R/C | 0.1419 | likely_benign | 0.1346 | benign | -0.481 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| R/D | 0.6697 | likely_pathogenic | 0.7038 | pathogenic | 0.043 | Stabilizing | 0.97 | D | 0.562 | neutral | None | None | None | None | N |
| R/E | 0.2849 | likely_benign | 0.3069 | benign | 0.205 | Stabilizing | 0.871 | D | 0.487 | neutral | None | None | None | None | N |
| R/F | 0.4888 | ambiguous | 0.4898 | ambiguous | -0.127 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | N |
| R/G | 0.2071 | likely_benign | 0.232 | benign | -0.913 | Destabilizing | 0.98 | D | 0.571 | neutral | N | 0.457547773 | None | None | N |
| R/H | 0.1146 | likely_benign | 0.1142 | benign | -1.278 | Destabilizing | 0.996 | D | 0.508 | neutral | None | None | None | None | N |
| R/I | 0.1967 | likely_benign | 0.2087 | benign | 0.406 | Stabilizing | 0.998 | D | 0.632 | neutral | N | 0.485678059 | None | None | N |
| R/K | 0.0891 | likely_benign | 0.0909 | benign | -0.562 | Destabilizing | 0.835 | D | 0.427 | neutral | N | 0.50476293 | None | None | N |
| R/L | 0.1741 | likely_benign | 0.1838 | benign | 0.406 | Stabilizing | 0.97 | D | 0.571 | neutral | None | None | None | None | N |
| R/M | 0.1989 | likely_benign | 0.21 | benign | -0.126 | Destabilizing | 0.999 | D | 0.564 | neutral | None | None | None | None | N |
| R/N | 0.5231 | ambiguous | 0.539 | ambiguous | -0.195 | Destabilizing | 0.985 | D | 0.511 | neutral | None | None | None | None | N |
| R/P | 0.8575 | likely_pathogenic | 0.8757 | pathogenic | 0.106 | Stabilizing | 0.999 | D | 0.564 | neutral | None | None | None | None | N |
| R/Q | 0.0818 | likely_benign | 0.084 | benign | -0.192 | Destabilizing | 0.348 | N | 0.116 | neutral | None | None | None | None | N |
| R/S | 0.3903 | ambiguous | 0.4161 | ambiguous | -0.843 | Destabilizing | 0.961 | D | 0.53 | neutral | N | 0.474093306 | None | None | N |
| R/T | 0.1518 | likely_benign | 0.1671 | benign | -0.483 | Destabilizing | 0.98 | D | 0.548 | neutral | N | 0.494929938 | None | None | N |
| R/V | 0.2288 | likely_benign | 0.2418 | benign | 0.106 | Stabilizing | 0.996 | D | 0.551 | neutral | None | None | None | None | N |
| R/W | 0.2056 | likely_benign | 0.2035 | benign | 0.174 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/Y | 0.3738 | ambiguous | 0.3678 | ambiguous | 0.438 | Stabilizing | 0.999 | D | 0.627 | 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.