Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32690 | 98293;98294;98295 | chr2:178540098;178540097;178540096 | chr2:179404825;179404824;179404823 |
| N2AB | 31049 | 93370;93371;93372 | chr2:178540098;178540097;178540096 | chr2:179404825;179404824;179404823 |
| N2A | 30122 | 90589;90590;90591 | chr2:178540098;178540097;178540096 | chr2:179404825;179404824;179404823 |
| N2B | 23625 | 71098;71099;71100 | chr2:178540098;178540097;178540096 | chr2:179404825;179404824;179404823 |
| Novex-1 | 23750 | 71473;71474;71475 | chr2:178540098;178540097;178540096 | chr2:179404825;179404824;179404823 |
| Novex-2 | 23817 | 71674;71675;71676 | chr2:178540098;178540097;178540096 | chr2:179404825;179404824;179404823 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1457945906  |
-0.053 | 1.0 | N | 0.697 | 0.386 | 0.796323768304 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9E-06 | 0 |
| P/S | rs1161513687 |
-0.293 | 1.0 | N | 0.757 | 0.314 | 0.349429436713 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1161513687 |
-0.293 | 1.0 | N | 0.757 | 0.314 | 0.349429436713 | gnomAD-4.0.0 | 1.60643E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77731E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0994 | likely_benign | 0.0983 | benign | -0.419 | Destabilizing | 0.999 | D | 0.755 | deleterious | N | 0.506195443 | None | None | N |
| P/C | 0.5157 | ambiguous | 0.5067 | ambiguous | -0.719 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| P/D | 0.4068 | ambiguous | 0.4122 | ambiguous | -0.31 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| P/E | 0.2584 | likely_benign | 0.2622 | benign | -0.419 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| P/F | 0.5137 | ambiguous | 0.5028 | ambiguous | -0.66 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| P/G | 0.3344 | likely_benign | 0.3277 | benign | -0.531 | Destabilizing | 1.0 | D | 0.729 | deleterious | None | None | None | None | N |
| P/H | 0.2422 | likely_benign | 0.2408 | benign | -0.106 | Destabilizing | 1.0 | D | 0.666 | prob.neutral | None | None | None | None | N |
| P/I | 0.3604 | ambiguous | 0.3554 | ambiguous | -0.269 | Destabilizing | 1.0 | D | 0.665 | prob.neutral | None | None | None | None | N |
| P/K | 0.2834 | likely_benign | 0.2871 | benign | -0.469 | Destabilizing | 1.0 | D | 0.738 | deleterious | None | None | None | None | N |
| P/L | 0.1431 | likely_benign | 0.141 | benign | -0.269 | Destabilizing | 1.0 | D | 0.697 | prob.delet. | N | 0.481916894 | None | None | N |
| P/M | 0.3264 | likely_benign | 0.3184 | benign | -0.465 | Destabilizing | 1.0 | D | 0.663 | prob.neutral | None | None | None | None | N |
| P/N | 0.3521 | ambiguous | 0.3468 | ambiguous | -0.251 | Destabilizing | 1.0 | D | 0.685 | prob.delet. | None | None | None | None | N |
| P/Q | 0.1789 | likely_benign | 0.1775 | benign | -0.469 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.492005751 | None | None | N |
| P/R | 0.2126 | likely_benign | 0.2236 | benign | 0.016 | Stabilizing | 1.0 | D | 0.667 | prob.neutral | N | 0.49728567 | None | None | N |
| P/S | 0.1467 | likely_benign | 0.1416 | benign | -0.583 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.461924591 | None | None | N |
| P/T | 0.1175 | likely_benign | 0.1151 | benign | -0.593 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.508080955 | None | None | N |
| P/V | 0.2479 | likely_benign | 0.2419 | benign | -0.286 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| P/W | 0.6426 | likely_pathogenic | 0.6512 | pathogenic | -0.743 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| P/Y | 0.4791 | ambiguous | 0.4812 | ambiguous | -0.451 | Destabilizing | 1.0 | D | 0.679 | prob.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.