Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17701 | 53326;53327;53328 | chr2:178607587;178607586;178607585 | chr2:179472314;179472313;179472312 |
| N2AB | 16060 | 48403;48404;48405 | chr2:178607587;178607586;178607585 | chr2:179472314;179472313;179472312 |
| N2A | 15133 | 45622;45623;45624 | chr2:178607587;178607586;178607585 | chr2:179472314;179472313;179472312 |
| N2B | 8636 | 26131;26132;26133 | chr2:178607587;178607586;178607585 | chr2:179472314;179472313;179472312 |
| Novex-1 | 8761 | 26506;26507;26508 | chr2:178607587;178607586;178607585 | chr2:179472314;179472313;179472312 |
| Novex-2 | 8828 | 26707;26708;26709 | chr2:178607587;178607586;178607585 | chr2:179472314;179472313;179472312 |
| 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/E | rs1484367786  |
-0.375 | 0.025 | N | 0.456 | 0.219 | 0.374255764437 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/E | rs1484367786 |
-0.375 | 0.025 | N | 0.456 | 0.219 | 0.374255764437 | gnomAD-4.0.0 | 4.77705E-06 | None | None | None | None | I | None | 0 | 4.57352E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02718E-05 |
| V/I | rs1481397518 |
None | None | N | 0.171 | 0.134 | 0.18995819373 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/I | rs1481397518 |
None | None | N | 0.171 | 0.134 | 0.18995819373 | gnomAD-4.0.0 | 6.19941E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.479E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1236 | likely_benign | 0.0943 | benign | -0.482 | Destabilizing | None | N | 0.141 | neutral | N | 0.424409139 | None | None | I |
| V/C | 0.6579 | likely_pathogenic | 0.5934 | pathogenic | -0.614 | Destabilizing | 0.54 | D | 0.425 | neutral | None | None | None | None | I |
| V/D | 0.2239 | likely_benign | 0.1512 | benign | -0.298 | Destabilizing | 0.001 | N | 0.276 | neutral | None | None | None | None | I |
| V/E | 0.2 | likely_benign | 0.1379 | benign | -0.419 | Destabilizing | 0.025 | N | 0.456 | neutral | N | 0.44736057 | None | None | I |
| V/F | 0.1503 | likely_benign | 0.137 | benign | -0.728 | Destabilizing | 0.076 | N | 0.453 | neutral | None | None | None | None | I |
| V/G | 0.2192 | likely_benign | 0.1658 | benign | -0.605 | Destabilizing | 0.025 | N | 0.44 | neutral | N | 0.491960207 | None | None | I |
| V/H | 0.4678 | ambiguous | 0.3894 | ambiguous | -0.197 | Destabilizing | 0.367 | N | 0.516 | neutral | None | None | None | None | I |
| V/I | 0.0761 | likely_benign | 0.0709 | benign | -0.311 | Destabilizing | None | N | 0.171 | neutral | N | 0.439533308 | None | None | I |
| V/K | 0.2773 | likely_benign | 0.2136 | benign | -0.443 | Destabilizing | 0.001 | N | 0.25 | neutral | None | None | None | None | I |
| V/L | 0.1464 | likely_benign | 0.1155 | benign | -0.311 | Destabilizing | 0.004 | N | 0.184 | neutral | N | 0.434260774 | None | None | I |
| V/M | 0.1312 | likely_benign | 0.1066 | benign | -0.345 | Destabilizing | 0.367 | N | 0.302 | neutral | None | None | None | None | I |
| V/N | 0.1738 | likely_benign | 0.1305 | benign | -0.174 | Destabilizing | 0.142 | N | 0.548 | neutral | None | None | None | None | I |
| V/P | 0.2565 | likely_benign | 0.1895 | benign | -0.333 | Destabilizing | 0.001 | N | 0.254 | neutral | None | None | None | None | I |
| V/Q | 0.2454 | likely_benign | 0.1908 | benign | -0.433 | Destabilizing | 0.142 | N | 0.551 | neutral | None | None | None | None | I |
| V/R | 0.277 | likely_benign | 0.2221 | benign | 0.081 | Stabilizing | 0.076 | N | 0.548 | neutral | None | None | None | None | I |
| V/S | 0.1424 | likely_benign | 0.1065 | benign | -0.524 | Destabilizing | 0.033 | N | 0.391 | neutral | None | None | None | None | I |
| V/T | 0.1391 | likely_benign | 0.1091 | benign | -0.547 | Destabilizing | 0.001 | N | 0.169 | neutral | None | None | None | None | I |
| V/W | 0.7724 | likely_pathogenic | 0.7063 | pathogenic | -0.8 | Destabilizing | 0.931 | D | 0.497 | neutral | None | None | None | None | I |
| V/Y | 0.4547 | ambiguous | 0.3929 | ambiguous | -0.502 | Destabilizing | 0.001 | N | 0.219 | neutral | None | None | None | None | I |
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.