Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20089 | 60490;60491;60492 | chr2:178591460;178591459;178591458 | chr2:179456187;179456186;179456185 |
| N2AB | 18448 | 55567;55568;55569 | chr2:178591460;178591459;178591458 | chr2:179456187;179456186;179456185 |
| N2A | 17521 | 52786;52787;52788 | chr2:178591460;178591459;178591458 | chr2:179456187;179456186;179456185 |
| N2B | 11024 | 33295;33296;33297 | chr2:178591460;178591459;178591458 | chr2:179456187;179456186;179456185 |
| Novex-1 | 11149 | 33670;33671;33672 | chr2:178591460;178591459;178591458 | chr2:179456187;179456186;179456185 |
| Novex-2 | 11216 | 33871;33872;33873 | chr2:178591460;178591459;178591458 | chr2:179456187;179456186;179456185 |
| 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/A | rs886039085  |
-0.497 | 0.91 | N | 0.469 | 0.217 | 0.557597400255 | gnomAD-2.1.1 | 1.76E-05 | None | None | None | None | I | None | 0 | 6.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 9.39E-06 | 1.81951E-04 |
| V/A | rs886039085 |
-0.497 | 0.91 | N | 0.469 | 0.217 | 0.557597400255 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs886039085 |
-0.497 | 0.91 | N | 0.469 | 0.217 | 0.557597400255 | gnomAD-4.0.0 | 2.32634E-05 | None | None | None | None | I | None | 0 | 7.31957E-05 | None | 0 | 0 | None | 0 | 1.67448E-04 | 2.47478E-05 | 0 | 4.87916E-05 |
| V/M | rs2050176457 |
None | 0.994 | D | 0.488 | 0.275 | None | gnomAD-4.0.0 | 1.65421E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.92694E-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 | 0.3586 | ambiguous | 0.2898 | benign | -0.634 | Destabilizing | 0.91 | D | 0.469 | neutral | N | 0.49940833 | None | None | I |
| V/C | 0.889 | likely_pathogenic | 0.8486 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.554 | neutral | None | None | None | None | I |
| V/D | 0.7682 | likely_pathogenic | 0.7013 | pathogenic | -0.211 | Destabilizing | 0.996 | D | 0.591 | neutral | None | None | None | None | I |
| V/E | 0.5741 | likely_pathogenic | 0.5105 | ambiguous | -0.273 | Destabilizing | 0.994 | D | 0.539 | neutral | N | 0.48986334 | None | None | I |
| V/F | 0.3633 | ambiguous | 0.3147 | benign | -0.568 | Destabilizing | 0.996 | D | 0.535 | neutral | None | None | None | None | I |
| V/G | 0.5767 | likely_pathogenic | 0.5032 | ambiguous | -0.822 | Destabilizing | 0.994 | D | 0.523 | neutral | N | 0.494508329 | None | None | I |
| V/H | 0.7806 | likely_pathogenic | 0.7126 | pathogenic | -0.208 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | I |
| V/I | 0.0886 | likely_benign | 0.082 | benign | -0.265 | Destabilizing | 0.155 | N | 0.134 | neutral | None | None | None | None | I |
| V/K | 0.6695 | likely_pathogenic | 0.5937 | pathogenic | -0.62 | Destabilizing | 0.996 | D | 0.547 | neutral | None | None | None | None | I |
| V/L | 0.3397 | likely_benign | 0.2741 | benign | -0.265 | Destabilizing | 0.835 | D | 0.394 | neutral | N | 0.50978004 | None | None | I |
| V/M | 0.2373 | likely_benign | 0.1953 | benign | -0.479 | Destabilizing | 0.994 | D | 0.488 | neutral | D | 0.530771387 | None | None | I |
| V/N | 0.5612 | ambiguous | 0.4547 | ambiguous | -0.509 | Destabilizing | 0.996 | D | 0.607 | neutral | None | None | None | None | I |
| V/P | 0.9028 | likely_pathogenic | 0.8573 | pathogenic | -0.352 | Destabilizing | 0.999 | D | 0.598 | neutral | None | None | None | None | I |
| V/Q | 0.5317 | ambiguous | 0.4676 | ambiguous | -0.662 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | I |
| V/R | 0.6247 | likely_pathogenic | 0.5634 | ambiguous | -0.131 | Destabilizing | 0.996 | D | 0.603 | neutral | None | None | None | None | I |
| V/S | 0.4194 | ambiguous | 0.3424 | ambiguous | -0.948 | Destabilizing | 0.942 | D | 0.522 | neutral | None | None | None | None | I |
| V/T | 0.2126 | likely_benign | 0.1731 | benign | -0.897 | Destabilizing | 0.304 | N | 0.2 | neutral | None | None | None | None | I |
| V/W | 0.9268 | likely_pathogenic | 0.9121 | pathogenic | -0.67 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| V/Y | 0.784 | likely_pathogenic | 0.7321 | pathogenic | -0.384 | Destabilizing | 0.999 | D | 0.535 | 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.