Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24922 | 74989;74990;74991 | chr2:178571368;178571367;178571366 | chr2:179436095;179436094;179436093 |
| N2AB | 23281 | 70066;70067;70068 | chr2:178571368;178571367;178571366 | chr2:179436095;179436094;179436093 |
| N2A | 22354 | 67285;67286;67287 | chr2:178571368;178571367;178571366 | chr2:179436095;179436094;179436093 |
| N2B | 15857 | 47794;47795;47796 | chr2:178571368;178571367;178571366 | chr2:179436095;179436094;179436093 |
| Novex-1 | 15982 | 48169;48170;48171 | chr2:178571368;178571367;178571366 | chr2:179436095;179436094;179436093 |
| Novex-2 | 16049 | 48370;48371;48372 | chr2:178571368;178571367;178571366 | chr2:179436095;179436094;179436093 |
| 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/M | rs1002914471  |
None | 0.56 | N | 0.439 | 0.083 | 0.176091768786 | 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 |
| R/M | rs1002914471 |
None | 0.56 | N | 0.439 | 0.083 | 0.176091768786 | gnomAD-4.0.0 | 6.57886E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47137E-05 | 0 | 0 |
| R/S | rs372814940 |
-0.947 | 0.012 | N | 0.443 | 0.047 | 0.117506650769 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.24E-05 | 0 |
| R/S | rs372814940 |
-0.947 | 0.012 | N | 0.443 | 0.047 | 0.117506650769 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/S | rs372814940 |
-0.947 | 0.012 | N | 0.443 | 0.047 | 0.117506650769 | gnomAD-4.0.0 | 3.71932E-05 | None | None | None | None | N | None | 0 | 3.336E-05 | None | 0 | 0 | None | 0 | 0 | 4.74765E-05 | 1.09806E-05 | 1.60164E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3045 | likely_benign | 0.3161 | benign | -0.711 | Destabilizing | 0.007 | N | 0.38 | neutral | None | None | None | None | N |
| R/C | 0.1923 | likely_benign | 0.2115 | benign | -0.644 | Destabilizing | 0.864 | D | 0.455 | neutral | None | None | None | None | N |
| R/D | 0.7254 | likely_pathogenic | 0.7499 | pathogenic | -0.34 | Destabilizing | 0.072 | N | 0.525 | neutral | None | None | None | None | N |
| R/E | 0.3807 | ambiguous | 0.3986 | ambiguous | -0.277 | Destabilizing | 0.016 | N | 0.319 | neutral | None | None | None | None | N |
| R/F | 0.5858 | likely_pathogenic | 0.6142 | pathogenic | -0.935 | Destabilizing | 0.356 | N | 0.489 | neutral | None | None | None | None | N |
| R/G | 0.2013 | likely_benign | 0.2129 | benign | -0.939 | Destabilizing | 0.024 | N | 0.485 | neutral | N | 0.443597041 | None | None | N |
| R/H | 0.1293 | likely_benign | 0.1302 | benign | -1.282 | Destabilizing | 0.356 | N | 0.348 | neutral | None | None | None | None | N |
| R/I | 0.3354 | likely_benign | 0.3572 | ambiguous | -0.125 | Destabilizing | 0.214 | N | 0.526 | neutral | None | None | None | None | N |
| R/K | 0.0662 | likely_benign | 0.0673 | benign | -0.793 | Destabilizing | None | N | 0.077 | neutral | N | 0.346974571 | None | None | N |
| R/L | 0.2827 | likely_benign | 0.3043 | benign | -0.125 | Destabilizing | 0.016 | N | 0.491 | neutral | None | None | None | None | N |
| R/M | 0.2695 | likely_benign | 0.2825 | benign | -0.203 | Destabilizing | 0.56 | D | 0.439 | neutral | N | 0.511958261 | None | None | N |
| R/N | 0.5521 | ambiguous | 0.5681 | pathogenic | -0.223 | Destabilizing | 0.072 | N | 0.292 | neutral | None | None | None | None | N |
| R/P | 0.5067 | ambiguous | 0.5571 | ambiguous | -0.301 | Destabilizing | 0.136 | N | 0.527 | neutral | None | None | None | None | N |
| R/Q | 0.1185 | likely_benign | 0.1221 | benign | -0.53 | Destabilizing | 0.038 | N | 0.33 | neutral | None | None | None | None | N |
| R/S | 0.4151 | ambiguous | 0.4854 | ambiguous | -0.88 | Destabilizing | 0.012 | N | 0.443 | neutral | N | 0.397283174 | None | None | N |
| R/T | 0.2853 | likely_benign | 0.3045 | benign | -0.674 | Destabilizing | None | N | 0.134 | neutral | N | 0.447925425 | None | None | N |
| R/V | 0.3875 | ambiguous | 0.4134 | ambiguous | -0.301 | Destabilizing | 0.038 | N | 0.534 | neutral | None | None | None | None | N |
| R/W | 0.2529 | likely_benign | 0.2679 | benign | -0.718 | Destabilizing | 0.828 | D | 0.461 | neutral | N | 0.469229191 | None | None | N |
| R/Y | 0.4625 | ambiguous | 0.4899 | ambiguous | -0.364 | Destabilizing | 0.356 | N | 0.455 | 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.