Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29796 | 89611;89612;89613 | chr2:178553619;178553618;178553617 | chr2:179418346;179418345;179418344 |
| N2AB | 28155 | 84688;84689;84690 | chr2:178553619;178553618;178553617 | chr2:179418346;179418345;179418344 |
| N2A | 27228 | 81907;81908;81909 | chr2:178553619;178553618;178553617 | chr2:179418346;179418345;179418344 |
| N2B | 20731 | 62416;62417;62418 | chr2:178553619;178553618;178553617 | chr2:179418346;179418345;179418344 |
| Novex-1 | 20856 | 62791;62792;62793 | chr2:178553619;178553618;178553617 | chr2:179418346;179418345;179418344 |
| Novex-2 | 20923 | 62992;62993;62994 | chr2:178553619;178553618;178553617 | chr2:179418346;179418345;179418344 |
| 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/M | rs72648237  |
-0.291 | 1.0 | N | 0.701 | 0.252 | None | gnomAD-2.1.1 | 1.18939E-03 | None | None | None | None | N | None | 1.23946E-04 | 5.93891E-04 | None | 3.29075E-03 | 0 | None | 5.45823E-03 | None | 0 | 7.35294E-04 | 1.96629E-03 |
| V/M | rs72648237 |
-0.291 | 1.0 | N | 0.701 | 0.252 | None | gnomAD-3.1.2 | 7.55704E-04 | None | None | None | None | N | None | 2.65354E-04 | 6.54793E-04 | 0 | 3.45622E-03 | 0 | None | 0 | 3.16456E-03 | 8.5269E-04 | 3.10302E-03 | 3.83142E-03 |
| V/M | rs72648237 |
-0.291 | 1.0 | N | 0.701 | 0.252 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 2E-03 | None |
| V/M | rs72648237 |
-0.291 | 1.0 | N | 0.701 | 0.252 | None | gnomAD-4.0.0 | 9.64759E-04 | None | None | None | None | N | None | 1.73218E-04 | 7.16476E-04 | None | 3.44595E-03 | 0 | None | 0 | 8.25355E-04 | 7.19615E-04 | 5.08322E-03 | 1.31246E-03 |
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 | 0.283 | likely_benign | 0.261 | benign | -0.898 | Destabilizing | 0.999 | D | 0.552 | neutral | N | 0.49579673 | None | None | N |
| V/C | 0.8107 | likely_pathogenic | 0.8145 | pathogenic | -0.792 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| V/D | 0.6213 | likely_pathogenic | 0.583 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| V/E | 0.3981 | ambiguous | 0.3795 | ambiguous | -0.263 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.485771737 | None | None | N |
| V/F | 0.4016 | ambiguous | 0.3925 | ambiguous | -0.722 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| V/G | 0.4371 | ambiguous | 0.4273 | ambiguous | -1.141 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.52063646 | None | None | N |
| V/H | 0.713 | likely_pathogenic | 0.7092 | pathogenic | -0.554 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| V/I | 0.0983 | likely_benign | 0.0966 | benign | -0.367 | Destabilizing | 0.998 | D | 0.463 | neutral | None | None | None | None | N |
| V/K | 0.437 | ambiguous | 0.4304 | ambiguous | -0.687 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| V/L | 0.3794 | ambiguous | 0.373 | ambiguous | -0.367 | Destabilizing | 0.997 | D | 0.481 | neutral | N | 0.483232865 | None | None | N |
| V/M | 0.2419 | likely_benign | 0.2334 | benign | -0.426 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.491660347 | None | None | N |
| V/N | 0.4418 | ambiguous | 0.426 | ambiguous | -0.496 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/P | 0.7834 | likely_pathogenic | 0.7857 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| V/Q | 0.4233 | ambiguous | 0.4267 | ambiguous | -0.646 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| V/R | 0.3968 | ambiguous | 0.3968 | ambiguous | -0.213 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| V/S | 0.3439 | ambiguous | 0.3313 | benign | -1.026 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| V/T | 0.1402 | likely_benign | 0.134 | benign | -0.947 | Destabilizing | 0.999 | D | 0.622 | neutral | None | None | None | None | N |
| V/W | 0.9357 | likely_pathogenic | 0.931 | pathogenic | -0.827 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| V/Y | 0.7675 | likely_pathogenic | 0.764 | pathogenic | -0.537 | Destabilizing | 1.0 | D | 0.806 | deleterious | 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.