Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25613 | 77062;77063;77064 | chr2:178569295;178569294;178569293 | chr2:179434022;179434021;179434020 |
| N2AB | 23972 | 72139;72140;72141 | chr2:178569295;178569294;178569293 | chr2:179434022;179434021;179434020 |
| N2A | 23045 | 69358;69359;69360 | chr2:178569295;178569294;178569293 | chr2:179434022;179434021;179434020 |
| N2B | 16548 | 49867;49868;49869 | chr2:178569295;178569294;178569293 | chr2:179434022;179434021;179434020 |
| Novex-1 | 16673 | 50242;50243;50244 | chr2:178569295;178569294;178569293 | chr2:179434022;179434021;179434020 |
| Novex-2 | 16740 | 50443;50444;50445 | chr2:178569295;178569294;178569293 | chr2:179434022;179434021;179434020 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs1553601096  |
None | 0.949 | N | 0.67 | 0.532 | 0.860775079401 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1707239042 |
None | 0.003 | N | 0.126 | 0.09 | 0.379366414296 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1707239042 |
None | 0.003 | N | 0.126 | 0.09 | 0.379366414296 | gnomAD-4.0.0 | 3.04496E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61492E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4464 | ambiguous | 0.4589 | ambiguous | -1.66 | Destabilizing | 0.415 | N | 0.54 | neutral | None | None | None | None | N |
| I/C | 0.6643 | likely_pathogenic | 0.6593 | pathogenic | -1.459 | Destabilizing | 0.996 | D | 0.522 | neutral | None | None | None | None | N |
| I/D | 0.8815 | likely_pathogenic | 0.8847 | pathogenic | -1.239 | Destabilizing | 0.987 | D | 0.665 | neutral | None | None | None | None | N |
| I/E | 0.759 | likely_pathogenic | 0.7679 | pathogenic | -1.231 | Destabilizing | 0.961 | D | 0.645 | neutral | None | None | None | None | N |
| I/F | 0.2717 | likely_benign | 0.2945 | benign | -1.32 | Destabilizing | 0.901 | D | 0.473 | neutral | N | 0.480704536 | None | None | N |
| I/G | 0.7755 | likely_pathogenic | 0.7897 | pathogenic | -1.958 | Destabilizing | 0.961 | D | 0.63 | neutral | None | None | None | None | N |
| I/H | 0.706 | likely_pathogenic | 0.7233 | pathogenic | -1.196 | Destabilizing | 0.996 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/K | 0.5207 | ambiguous | 0.544 | ambiguous | -1.004 | Destabilizing | 0.923 | D | 0.645 | neutral | None | None | None | None | N |
| I/L | 0.1802 | likely_benign | 0.192 | benign | -0.916 | Destabilizing | 0.075 | N | 0.276 | neutral | N | 0.486235884 | None | None | N |
| I/M | 0.1191 | likely_benign | 0.1226 | benign | -0.957 | Destabilizing | 0.156 | N | 0.348 | neutral | N | 0.491464957 | None | None | N |
| I/N | 0.4205 | ambiguous | 0.411 | ambiguous | -0.918 | Destabilizing | 0.949 | D | 0.67 | neutral | N | 0.502060794 | None | None | N |
| I/P | 0.8813 | likely_pathogenic | 0.9014 | pathogenic | -1.135 | Destabilizing | 0.987 | D | 0.667 | neutral | None | None | None | None | N |
| I/Q | 0.5954 | likely_pathogenic | 0.6087 | pathogenic | -1.133 | Destabilizing | 0.961 | D | 0.675 | neutral | None | None | None | None | N |
| I/R | 0.4759 | ambiguous | 0.4923 | ambiguous | -0.501 | Destabilizing | 0.923 | D | 0.669 | neutral | None | None | None | None | N |
| I/S | 0.4623 | ambiguous | 0.4532 | ambiguous | -1.558 | Destabilizing | 0.901 | D | 0.539 | neutral | N | 0.476968326 | None | None | N |
| I/T | 0.2677 | likely_benign | 0.276 | benign | -1.434 | Destabilizing | 0.722 | D | 0.491 | neutral | N | 0.491161701 | None | None | N |
| I/V | 0.0699 | likely_benign | 0.0699 | benign | -1.135 | Destabilizing | 0.003 | N | 0.126 | neutral | N | 0.391245423 | None | None | N |
| I/W | 0.8784 | likely_pathogenic | 0.8868 | pathogenic | -1.33 | Destabilizing | 0.996 | D | 0.745 | deleterious | None | None | None | None | N |
| I/Y | 0.6329 | likely_pathogenic | 0.6506 | pathogenic | -1.061 | Destabilizing | 0.961 | D | 0.539 | 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.