Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23739 | 71440;71441;71442 | chr2:178574917;178574916;178574915 | chr2:179439644;179439643;179439642 |
| N2AB | 22098 | 66517;66518;66519 | chr2:178574917;178574916;178574915 | chr2:179439644;179439643;179439642 |
| N2A | 21171 | 63736;63737;63738 | chr2:178574917;178574916;178574915 | chr2:179439644;179439643;179439642 |
| N2B | 14674 | 44245;44246;44247 | chr2:178574917;178574916;178574915 | chr2:179439644;179439643;179439642 |
| Novex-1 | 14799 | 44620;44621;44622 | chr2:178574917;178574916;178574915 | chr2:179439644;179439643;179439642 |
| Novex-2 | 14866 | 44821;44822;44823 | chr2:178574917;178574916;178574915 | chr2:179439644;179439643;179439642 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs374485278  |
-1.26 | 0.638 | N | 0.739 | 0.267 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs374485278 |
-1.26 | 0.638 | N | 0.739 | 0.267 | None | 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 |
| V/F | rs374485278 |
-1.26 | 0.638 | N | 0.739 | 0.267 | None | gnomAD-4.0.0 | 3.04486E-06 | None | None | None | None | N | None | 5.23158E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4052 | ambiguous | 0.4554 | ambiguous | -1.46 | Destabilizing | 0.334 | N | 0.426 | neutral | N | 0.47063845 | None | None | N |
| V/C | 0.7737 | likely_pathogenic | 0.8206 | pathogenic | -1.265 | Destabilizing | 0.982 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/D | 0.794 | likely_pathogenic | 0.8271 | pathogenic | -0.839 | Destabilizing | 0.781 | D | 0.81 | deleterious | N | 0.503328241 | None | None | N |
| V/E | 0.5929 | likely_pathogenic | 0.6548 | pathogenic | -0.735 | Destabilizing | 0.826 | D | 0.751 | deleterious | None | None | None | None | N |
| V/F | 0.3127 | likely_benign | 0.3418 | ambiguous | -0.933 | Destabilizing | 0.638 | D | 0.739 | prob.delet. | N | 0.490276869 | None | None | N |
| V/G | 0.5492 | ambiguous | 0.5809 | pathogenic | -1.874 | Destabilizing | 0.781 | D | 0.795 | deleterious | N | 0.512900575 | None | None | N |
| V/H | 0.8122 | likely_pathogenic | 0.8528 | pathogenic | -1.48 | Destabilizing | 0.982 | D | 0.796 | deleterious | None | None | None | None | N |
| V/I | 0.0623 | likely_benign | 0.0659 | benign | -0.382 | Destabilizing | 0.002 | N | 0.199 | neutral | N | 0.459972003 | None | None | N |
| V/K | 0.5625 | ambiguous | 0.6324 | pathogenic | -0.942 | Destabilizing | 0.826 | D | 0.751 | deleterious | None | None | None | None | N |
| V/L | 0.2645 | likely_benign | 0.3268 | benign | -0.382 | Destabilizing | 0.034 | N | 0.311 | neutral | N | 0.472751591 | None | None | N |
| V/M | 0.1975 | likely_benign | 0.2373 | benign | -0.576 | Destabilizing | 0.7 | D | 0.653 | neutral | None | None | None | None | N |
| V/N | 0.5829 | likely_pathogenic | 0.6547 | pathogenic | -0.923 | Destabilizing | 0.935 | D | 0.805 | deleterious | None | None | None | None | N |
| V/P | 0.8953 | likely_pathogenic | 0.9102 | pathogenic | -0.707 | Destabilizing | 0.935 | D | 0.773 | deleterious | None | None | None | None | N |
| V/Q | 0.575 | likely_pathogenic | 0.637 | pathogenic | -0.907 | Destabilizing | 0.935 | D | 0.767 | deleterious | None | None | None | None | N |
| V/R | 0.5498 | ambiguous | 0.6065 | pathogenic | -0.767 | Destabilizing | 0.826 | D | 0.804 | deleterious | None | None | None | None | N |
| V/S | 0.5176 | ambiguous | 0.5789 | pathogenic | -1.654 | Destabilizing | 0.826 | D | 0.751 | deleterious | None | None | None | None | N |
| V/T | 0.3485 | ambiguous | 0.4214 | ambiguous | -1.41 | Destabilizing | 0.399 | N | 0.532 | neutral | None | None | None | None | N |
| V/W | 0.9204 | likely_pathogenic | 0.9361 | pathogenic | -1.18 | Destabilizing | 0.982 | D | 0.796 | deleterious | None | None | None | None | N |
| V/Y | 0.6954 | likely_pathogenic | 0.7315 | pathogenic | -0.812 | Destabilizing | 0.826 | D | 0.758 | deleterious | 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.