Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32076 | 96451;96452;96453 | chr2:178543918;178543917;178543916 | chr2:179408645;179408644;179408643 |
| N2AB | 30435 | 91528;91529;91530 | chr2:178543918;178543917;178543916 | chr2:179408645;179408644;179408643 |
| N2A | 29508 | 88747;88748;88749 | chr2:178543918;178543917;178543916 | chr2:179408645;179408644;179408643 |
| N2B | 23011 | 69256;69257;69258 | chr2:178543918;178543917;178543916 | chr2:179408645;179408644;179408643 |
| Novex-1 | 23136 | 69631;69632;69633 | chr2:178543918;178543917;178543916 | chr2:179408645;179408644;179408643 |
| Novex-2 | 23203 | 69832;69833;69834 | chr2:178543918;178543917;178543916 | chr2:179408645;179408644;179408643 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs373289373  |
-0.519 | 0.489 | N | 0.231 | 0.175 | None | gnomAD-2.1.1 | 1.78E-05 | None | None | None | None | N | None | 2.06629E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs373289373 |
-0.519 | 0.489 | N | 0.231 | 0.175 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20656E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs373289373 |
-0.519 | 0.489 | N | 0.231 | 0.175 | None | gnomAD-4.0.0 | 5.57749E-06 | None | None | None | None | N | None | 1.2016E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.6112 | likely_pathogenic | 0.5898 | pathogenic | -0.91 | Destabilizing | 0.942 | D | 0.485 | neutral | None | None | None | None | N |
| N/C | 0.4633 | ambiguous | 0.4293 | ambiguous | 0.083 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| N/D | 0.1793 | likely_benign | 0.177 | benign | -0.454 | Destabilizing | 0.961 | D | 0.401 | neutral | N | 0.477896908 | None | None | N |
| N/E | 0.7826 | likely_pathogenic | 0.7541 | pathogenic | -0.363 | Destabilizing | 0.97 | D | 0.345 | neutral | None | None | None | None | N |
| N/F | 0.8299 | likely_pathogenic | 0.8009 | pathogenic | -0.68 | Destabilizing | 0.996 | D | 0.633 | neutral | None | None | None | None | N |
| N/G | 0.4453 | ambiguous | 0.419 | ambiguous | -1.251 | Destabilizing | 0.97 | D | 0.375 | neutral | None | None | None | None | N |
| N/H | 0.1892 | likely_benign | 0.1678 | benign | -1.028 | Destabilizing | 0.151 | N | 0.274 | neutral | N | 0.506046301 | None | None | N |
| N/I | 0.7327 | likely_pathogenic | 0.6918 | pathogenic | -0.041 | Destabilizing | 0.989 | D | 0.627 | neutral | D | 0.534867698 | None | None | N |
| N/K | 0.7915 | likely_pathogenic | 0.7558 | pathogenic | -0.311 | Destabilizing | 0.961 | D | 0.392 | neutral | N | 0.471122864 | None | None | N |
| N/L | 0.5767 | likely_pathogenic | 0.5191 | ambiguous | -0.041 | Destabilizing | 0.97 | D | 0.556 | neutral | None | None | None | None | N |
| N/M | 0.6427 | likely_pathogenic | 0.6125 | pathogenic | 0.439 | Stabilizing | 1.0 | D | 0.576 | neutral | None | None | None | None | N |
| N/P | 0.9622 | likely_pathogenic | 0.9484 | pathogenic | -0.301 | Destabilizing | 0.996 | D | 0.575 | neutral | None | None | None | None | N |
| N/Q | 0.7087 | likely_pathogenic | 0.673 | pathogenic | -0.834 | Destabilizing | 0.996 | D | 0.437 | neutral | None | None | None | None | N |
| N/R | 0.813 | likely_pathogenic | 0.78 | pathogenic | -0.374 | Destabilizing | 0.991 | D | 0.411 | neutral | None | None | None | None | N |
| N/S | 0.1117 | likely_benign | 0.1091 | benign | -0.888 | Destabilizing | 0.489 | N | 0.231 | neutral | N | 0.44701664 | None | None | N |
| N/T | 0.1862 | likely_benign | 0.1805 | benign | -0.603 | Destabilizing | 0.248 | N | 0.24 | neutral | N | 0.429334957 | None | None | N |
| N/V | 0.6863 | likely_pathogenic | 0.6612 | pathogenic | -0.301 | Destabilizing | 0.991 | D | 0.559 | neutral | None | None | None | None | N |
| N/W | 0.9451 | likely_pathogenic | 0.9283 | pathogenic | -0.462 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| N/Y | 0.4775 | ambiguous | 0.4322 | ambiguous | -0.267 | Destabilizing | 0.989 | D | 0.59 | neutral | N | 0.503925623 | 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.