Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23826 | 71701;71702;71703 | chr2:178574656;178574655;178574654 | chr2:179439383;179439382;179439381 |
| N2AB | 22185 | 66778;66779;66780 | chr2:178574656;178574655;178574654 | chr2:179439383;179439382;179439381 |
| N2A | 21258 | 63997;63998;63999 | chr2:178574656;178574655;178574654 | chr2:179439383;179439382;179439381 |
| N2B | 14761 | 44506;44507;44508 | chr2:178574656;178574655;178574654 | chr2:179439383;179439382;179439381 |
| Novex-1 | 14886 | 44881;44882;44883 | chr2:178574656;178574655;178574654 | chr2:179439383;179439382;179439381 |
| Novex-2 | 14953 | 45082;45083;45084 | chr2:178574656;178574655;178574654 | chr2:179439383;179439382;179439381 |
| 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/F | rs377751708  |
-0.891 | 0.994 | N | 0.545 | 0.32 | 0.764459265346 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.56E-05 | None | 0 | 0 | 0 |
| V/F | rs377751708 |
-0.891 | 0.994 | N | 0.545 | 0.32 | 0.764459265346 | gnomAD-4.0.0 | 2.73806E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99727E-07 | 3.48262E-05 | 0 |
| V/L | rs377751708 |
-0.099 | 0.745 | N | 0.391 | 0.138 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| V/L | rs377751708 |
-0.099 | 0.745 | N | 0.391 | 0.138 | None | gnomAD-4.0.0 | 2.87496E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.77885E-05 | 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 | 0.1783 | likely_benign | 0.1725 | benign | -0.462 | Destabilizing | 0.877 | D | 0.399 | neutral | N | 0.478688263 | None | None | I |
| V/C | 0.7487 | likely_pathogenic | 0.7382 | pathogenic | -0.613 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | I |
| V/D | 0.5392 | ambiguous | 0.549 | ambiguous | -0.127 | Destabilizing | 0.926 | D | 0.591 | neutral | N | 0.481951395 | None | None | I |
| V/E | 0.2698 | likely_benign | 0.2969 | benign | -0.246 | Destabilizing | 0.064 | N | 0.357 | neutral | None | None | None | None | I |
| V/F | 0.3196 | likely_benign | 0.2926 | benign | -0.882 | Destabilizing | 0.994 | D | 0.545 | neutral | N | 0.48853476 | None | None | I |
| V/G | 0.3457 | ambiguous | 0.3169 | benign | -0.56 | Destabilizing | 0.961 | D | 0.63 | neutral | N | 0.499891066 | None | None | I |
| V/H | 0.6919 | likely_pathogenic | 0.6965 | pathogenic | -0.232 | Destabilizing | 0.996 | D | 0.749 | deleterious | None | None | None | None | I |
| V/I | 0.0784 | likely_benign | 0.076 | benign | -0.36 | Destabilizing | 0.856 | D | 0.43 | neutral | N | 0.493697787 | None | None | I |
| V/K | 0.4147 | ambiguous | 0.4044 | ambiguous | -0.13 | Destabilizing | 0.943 | D | 0.534 | neutral | None | None | None | None | I |
| V/L | 0.2261 | likely_benign | 0.2207 | benign | -0.36 | Destabilizing | 0.745 | D | 0.391 | neutral | N | 0.481941999 | None | None | I |
| V/M | 0.1678 | likely_benign | 0.1587 | benign | -0.232 | Destabilizing | 0.995 | D | 0.544 | neutral | None | None | None | None | I |
| V/N | 0.382 | ambiguous | 0.3695 | ambiguous | 0.055 | Stabilizing | 0.971 | D | 0.799 | deleterious | None | None | None | None | I |
| V/P | 0.2774 | likely_benign | 0.2506 | benign | -0.361 | Destabilizing | 0.985 | D | 0.799 | deleterious | None | None | None | None | I |
| V/Q | 0.3447 | ambiguous | 0.354 | ambiguous | -0.232 | Destabilizing | 0.943 | D | 0.797 | deleterious | None | None | None | None | I |
| V/R | 0.4411 | ambiguous | 0.4278 | ambiguous | 0.306 | Stabilizing | 0.971 | D | 0.795 | deleterious | None | None | None | None | I |
| V/S | 0.2786 | likely_benign | 0.2705 | benign | -0.328 | Destabilizing | 0.971 | D | 0.531 | neutral | None | None | None | None | I |
| V/T | 0.1926 | likely_benign | 0.1897 | benign | -0.352 | Destabilizing | 0.904 | D | 0.624 | neutral | None | None | None | None | I |
| V/W | 0.9103 | likely_pathogenic | 0.9042 | pathogenic | -0.926 | Destabilizing | 0.999 | D | 0.748 | deleterious | None | None | None | None | I |
| V/Y | 0.6663 | likely_pathogenic | 0.6471 | pathogenic | -0.573 | Destabilizing | 0.995 | D | 0.546 | 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.