Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25189 | 75790;75791;75792 | chr2:178570567;178570566;178570565 | chr2:179435294;179435293;179435292 |
| N2AB | 23548 | 70867;70868;70869 | chr2:178570567;178570566;178570565 | chr2:179435294;179435293;179435292 |
| N2A | 22621 | 68086;68087;68088 | chr2:178570567;178570566;178570565 | chr2:179435294;179435293;179435292 |
| N2B | 16124 | 48595;48596;48597 | chr2:178570567;178570566;178570565 | chr2:179435294;179435293;179435292 |
| Novex-1 | 16249 | 48970;48971;48972 | chr2:178570567;178570566;178570565 | chr2:179435294;179435293;179435292 |
| Novex-2 | 16316 | 49171;49172;49173 | chr2:178570567;178570566;178570565 | chr2:179435294;179435293;179435292 |
| 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/I | rs757224932  |
0.051 | 0.997 | N | 0.371 | 0.182 | 0.605332244828 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/I | rs757224932 |
0.051 | 0.997 | N | 0.371 | 0.182 | 0.605332244828 | gnomAD-4.0.0 | 3.18431E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41663E-04 | 0 | 0 | 3.02718E-05 |
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 | 0.2046 | likely_benign | 0.2282 | benign | -0.363 | Destabilizing | 0.999 | D | 0.385 | neutral | N | 0.462503381 | None | None | I |
| V/C | 0.8297 | likely_pathogenic | 0.8611 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.596 | neutral | None | None | None | None | I |
| V/D | 0.5206 | ambiguous | 0.5967 | pathogenic | -0.346 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | D | 0.524610632 | None | None | I |
| V/E | 0.482 | ambiguous | 0.5658 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | I |
| V/F | 0.2803 | likely_benign | 0.319 | benign | -0.747 | Destabilizing | 1.0 | D | 0.599 | neutral | N | 0.487187267 | None | None | I |
| V/G | 0.367 | ambiguous | 0.4119 | ambiguous | -0.418 | Destabilizing | 1.0 | D | 0.646 | neutral | N | 0.509526537 | None | None | I |
| V/H | 0.7284 | likely_pathogenic | 0.7791 | pathogenic | -0.025 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| V/I | 0.0858 | likely_benign | 0.0836 | benign | -0.359 | Destabilizing | 0.997 | D | 0.371 | neutral | N | 0.462908813 | None | None | I |
| V/K | 0.5502 | ambiguous | 0.6309 | pathogenic | -0.386 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | I |
| V/L | 0.3111 | likely_benign | 0.3406 | ambiguous | -0.359 | Destabilizing | 0.997 | D | 0.411 | neutral | N | 0.502965924 | None | None | I |
| V/M | 0.2138 | likely_benign | 0.2297 | benign | -0.552 | Destabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | I |
| V/N | 0.4415 | ambiguous | 0.4881 | ambiguous | -0.205 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| V/P | 0.5046 | ambiguous | 0.5327 | ambiguous | -0.332 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| V/Q | 0.5246 | ambiguous | 0.5834 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| V/R | 0.4784 | ambiguous | 0.5722 | pathogenic | 0.073 | Stabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| V/S | 0.3163 | likely_benign | 0.352 | ambiguous | -0.515 | Destabilizing | 1.0 | D | 0.626 | neutral | None | None | None | None | I |
| V/T | 0.2406 | likely_benign | 0.2546 | benign | -0.543 | Destabilizing | 0.999 | D | 0.521 | neutral | None | None | None | None | I |
| V/W | 0.9152 | likely_pathogenic | 0.9307 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| V/Y | 0.705 | likely_pathogenic | 0.7581 | pathogenic | -0.524 | Destabilizing | 1.0 | D | 0.597 | 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.