Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19531 | 58816;58817;58818 | chr2:178593709;178593708;178593707 | chr2:179458436;179458435;179458434 |
| N2AB | 17890 | 53893;53894;53895 | chr2:178593709;178593708;178593707 | chr2:179458436;179458435;179458434 |
| N2A | 16963 | 51112;51113;51114 | chr2:178593709;178593708;178593707 | chr2:179458436;179458435;179458434 |
| N2B | 10466 | 31621;31622;31623 | chr2:178593709;178593708;178593707 | chr2:179458436;179458435;179458434 |
| Novex-1 | 10591 | 31996;31997;31998 | chr2:178593709;178593708;178593707 | chr2:179458436;179458435;179458434 |
| Novex-2 | 10658 | 32197;32198;32199 | chr2:178593709;178593708;178593707 | chr2:179458436;179458435;179458434 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1258679826  |
None | 0.638 | N | 0.709 | 0.297 | 0.357724736475 | gnomAD-4.0.0 | 1.36873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73611E-04 | 0 | 1.15955E-05 | 0 |
| T/R | rs1258679826 |
-0.135 | 0.638 | N | 0.724 | 0.331 | 0.503683571763 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| T/R | rs1258679826 |
-0.135 | 0.638 | N | 0.724 | 0.331 | 0.503683571763 | gnomAD-4.0.0 | 6.84366E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87371E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1689 | likely_benign | 0.1395 | benign | -0.572 | Destabilizing | 0.094 | N | 0.442 | neutral | N | 0.458723996 | None | None | N |
| T/C | 0.5855 | likely_pathogenic | 0.5536 | ambiguous | -0.383 | Destabilizing | 0.947 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/D | 0.7387 | likely_pathogenic | 0.7051 | pathogenic | 0.204 | Stabilizing | 0.539 | D | 0.629 | neutral | None | None | None | None | N |
| T/E | 0.7283 | likely_pathogenic | 0.6921 | pathogenic | 0.162 | Stabilizing | 0.539 | D | 0.641 | neutral | None | None | None | None | N |
| T/F | 0.5479 | ambiguous | 0.5091 | ambiguous | -0.885 | Destabilizing | 0.826 | D | 0.739 | prob.delet. | None | None | None | None | N |
| T/G | 0.449 | ambiguous | 0.4578 | ambiguous | -0.762 | Destabilizing | 0.25 | N | 0.567 | neutral | None | None | None | None | N |
| T/H | 0.5829 | likely_pathogenic | 0.5326 | ambiguous | -1.075 | Destabilizing | 0.947 | D | 0.719 | prob.delet. | None | None | None | None | N |
| T/I | 0.4899 | ambiguous | 0.4254 | ambiguous | -0.179 | Destabilizing | 0.638 | D | 0.709 | prob.delet. | N | 0.504803002 | None | None | N |
| T/K | 0.6691 | likely_pathogenic | 0.6234 | pathogenic | -0.476 | Destabilizing | 0.468 | N | 0.641 | neutral | N | 0.485601166 | None | None | N |
| T/L | 0.2243 | likely_benign | 0.1959 | benign | -0.179 | Destabilizing | 0.399 | N | 0.537 | neutral | None | None | None | None | N |
| T/M | 0.1804 | likely_benign | 0.1467 | benign | 0.03 | Stabilizing | 0.982 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/N | 0.2301 | likely_benign | 0.2258 | benign | -0.332 | Destabilizing | 0.539 | D | 0.607 | neutral | None | None | None | None | N |
| T/P | 0.6632 | likely_pathogenic | 0.6469 | pathogenic | -0.279 | Destabilizing | 0.638 | D | 0.715 | prob.delet. | N | 0.499205182 | None | None | N |
| T/Q | 0.568 | likely_pathogenic | 0.5203 | ambiguous | -0.53 | Destabilizing | 0.7 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/R | 0.6007 | likely_pathogenic | 0.5372 | ambiguous | -0.245 | Destabilizing | 0.638 | D | 0.724 | prob.delet. | N | 0.507149874 | None | None | N |
| T/S | 0.1612 | likely_benign | 0.1541 | benign | -0.606 | Destabilizing | 0.002 | N | 0.235 | neutral | N | 0.409428539 | None | None | N |
| T/V | 0.366 | ambiguous | 0.3129 | benign | -0.279 | Destabilizing | 0.399 | N | 0.501 | neutral | None | None | None | None | N |
| T/W | 0.8836 | likely_pathogenic | 0.8751 | pathogenic | -0.835 | Destabilizing | 0.982 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/Y | 0.6143 | likely_pathogenic | 0.574 | pathogenic | -0.576 | Destabilizing | 0.826 | D | 0.738 | prob.delet. | 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.