Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22743 | 68452;68453;68454 | chr2:178578713;178578712;178578711 | chr2:179443440;179443439;179443438 |
| N2AB | 21102 | 63529;63530;63531 | chr2:178578713;178578712;178578711 | chr2:179443440;179443439;179443438 |
| N2A | 20175 | 60748;60749;60750 | chr2:178578713;178578712;178578711 | chr2:179443440;179443439;179443438 |
| N2B | 13678 | 41257;41258;41259 | chr2:178578713;178578712;178578711 | chr2:179443440;179443439;179443438 |
| Novex-1 | 13803 | 41632;41633;41634 | chr2:178578713;178578712;178578711 | chr2:179443440;179443439;179443438 |
| Novex-2 | 13870 | 41833;41834;41835 | chr2:178578713;178578712;178578711 | chr2:179443440;179443439;179443438 |
| 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 | rs377290384  |
-0.274 | 0.988 | N | 0.487 | 0.346 | 0.786233052337 | gnomAD-2.1.1 | 8.23E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 1.69377E-04 |
| V/E | rs377290384 |
-0.274 | 0.988 | N | 0.487 | 0.346 | 0.786233052337 | gnomAD-4.0.0 | 2.7459E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60225E-06 | 0 | 0 |
| V/G | rs377290384 |
-0.492 | 0.851 | N | 0.533 | 0.32 | None | gnomAD-2.1.1 | 1.23E-05 | None | None | None | None | I | None | 1.95797E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/G | rs377290384 |
-0.492 | 0.851 | N | 0.533 | 0.32 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | rs377290384 |
-0.492 | 0.851 | N | 0.533 | 0.32 | None | gnomAD-4.0.0 | 3.72953E-06 | None | None | None | None | I | None | 8.05758E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs1444424656 |
None | 0.996 | N | 0.472 | 0.234 | 0.48763082235 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/M | rs1444424656 |
None | 0.996 | N | 0.472 | 0.234 | 0.48763082235 | gnomAD-4.0.0 | 2.58065E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.80312E-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 | 0.2043 | likely_benign | 0.2086 | benign | -0.579 | Destabilizing | 0.132 | N | 0.306 | neutral | N | 0.490270693 | None | None | I |
| V/C | 0.7713 | likely_pathogenic | 0.7343 | pathogenic | -0.617 | Destabilizing | 0.999 | D | 0.537 | neutral | None | None | None | None | I |
| V/D | 0.699 | likely_pathogenic | 0.748 | pathogenic | -0.338 | Destabilizing | 0.991 | D | 0.727 | deleterious | None | None | None | None | I |
| V/E | 0.4284 | ambiguous | 0.4619 | ambiguous | -0.462 | Destabilizing | 0.988 | D | 0.487 | neutral | N | 0.473290888 | None | None | I |
| V/F | 0.3722 | ambiguous | 0.3701 | ambiguous | -0.94 | Destabilizing | 0.997 | D | 0.459 | neutral | None | None | None | None | I |
| V/G | 0.4169 | ambiguous | 0.4394 | ambiguous | -0.696 | Destabilizing | 0.851 | D | 0.533 | neutral | N | 0.514868222 | None | None | I |
| V/H | 0.7627 | likely_pathogenic | 0.761 | pathogenic | -0.291 | Destabilizing | 0.999 | D | 0.723 | deleterious | None | None | None | None | I |
| V/I | 0.0819 | likely_benign | 0.0762 | benign | -0.423 | Destabilizing | 0.968 | D | 0.559 | neutral | None | None | None | None | I |
| V/K | 0.4311 | ambiguous | 0.4611 | ambiguous | -0.272 | Destabilizing | 0.981 | D | 0.503 | neutral | None | None | None | None | I |
| V/L | 0.3251 | likely_benign | 0.3011 | benign | -0.423 | Destabilizing | 0.824 | D | 0.615 | neutral | N | 0.465213038 | None | None | I |
| V/M | 0.2081 | likely_benign | 0.1955 | benign | -0.269 | Destabilizing | 0.996 | D | 0.472 | neutral | N | 0.497270946 | None | None | I |
| V/N | 0.4872 | ambiguous | 0.4915 | ambiguous | -0.037 | Destabilizing | 0.997 | D | 0.739 | deleterious | None | None | None | None | I |
| V/P | 0.3511 | ambiguous | 0.3936 | ambiguous | -0.441 | Destabilizing | 0.045 | N | 0.389 | neutral | None | None | None | None | I |
| V/Q | 0.4353 | ambiguous | 0.4343 | ambiguous | -0.353 | Destabilizing | 0.997 | D | 0.636 | neutral | None | None | None | None | I |
| V/R | 0.4382 | ambiguous | 0.466 | ambiguous | 0.246 | Stabilizing | 0.991 | D | 0.731 | deleterious | None | None | None | None | I |
| V/S | 0.3356 | likely_benign | 0.3357 | benign | -0.419 | Destabilizing | 0.883 | D | 0.434 | neutral | None | None | None | None | I |
| V/T | 0.2239 | likely_benign | 0.2151 | benign | -0.448 | Destabilizing | 0.938 | D | 0.519 | neutral | None | None | None | None | I |
| V/W | 0.9492 | likely_pathogenic | 0.9453 | pathogenic | -0.971 | Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | I |
| V/Y | 0.7686 | likely_pathogenic | 0.7682 | pathogenic | -0.639 | Destabilizing | 0.997 | D | 0.459 | 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.