Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25416 | 76471;76472;76473 | chr2:178569886;178569885;178569884 | chr2:179434613;179434612;179434611 |
| N2AB | 23775 | 71548;71549;71550 | chr2:178569886;178569885;178569884 | chr2:179434613;179434612;179434611 |
| N2A | 22848 | 68767;68768;68769 | chr2:178569886;178569885;178569884 | chr2:179434613;179434612;179434611 |
| N2B | 16351 | 49276;49277;49278 | chr2:178569886;178569885;178569884 | chr2:179434613;179434612;179434611 |
| Novex-1 | 16476 | 49651;49652;49653 | chr2:178569886;178569885;178569884 | chr2:179434613;179434612;179434611 |
| Novex-2 | 16543 | 49852;49853;49854 | chr2:178569886;178569885;178569884 | chr2:179434613;179434612;179434611 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs781781445  |
0.063 | 0.978 | N | 0.419 | 0.303 | 0.225902525712 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| D/E | rs781781445 |
0.063 | 0.978 | N | 0.419 | 0.303 | 0.225902525712 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/E | rs781781445 |
0.063 | 0.978 | N | 0.419 | 0.303 | 0.225902525712 | gnomAD-4.0.0 | 4.95884E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93412E-06 | 0 | 1.60174E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7594 | likely_pathogenic | 0.7247 | pathogenic | -0.179 | Destabilizing | 0.989 | D | 0.601 | neutral | N | 0.469215964 | None | None | N |
| D/C | 0.9662 | likely_pathogenic | 0.9589 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/E | 0.659 | likely_pathogenic | 0.6341 | pathogenic | -0.29 | Destabilizing | 0.978 | D | 0.419 | neutral | N | 0.506261653 | None | None | N |
| D/F | 0.973 | likely_pathogenic | 0.9648 | pathogenic | 0.388 | Stabilizing | 0.99 | D | 0.75 | deleterious | None | None | None | None | N |
| D/G | 0.6056 | likely_pathogenic | 0.5753 | pathogenic | -0.478 | Destabilizing | 0.978 | D | 0.569 | neutral | N | 0.485207079 | None | None | N |
| D/H | 0.8729 | likely_pathogenic | 0.8297 | pathogenic | 0.585 | Stabilizing | 0.994 | D | 0.699 | prob.neutral | N | 0.501224646 | None | None | N |
| D/I | 0.9694 | likely_pathogenic | 0.9611 | pathogenic | 0.59 | Stabilizing | 0.998 | D | 0.748 | deleterious | None | None | None | None | N |
| D/K | 0.9427 | likely_pathogenic | 0.9317 | pathogenic | 0.278 | Stabilizing | 0.995 | D | 0.663 | neutral | None | None | None | None | N |
| D/L | 0.9429 | likely_pathogenic | 0.9284 | pathogenic | 0.59 | Stabilizing | 0.995 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/M | 0.9792 | likely_pathogenic | 0.9721 | pathogenic | 0.586 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| D/N | 0.3374 | likely_benign | 0.2824 | benign | -0.451 | Destabilizing | 0.576 | D | 0.189 | neutral | D | 0.523655335 | None | None | N |
| D/P | 0.9955 | likely_pathogenic | 0.9932 | pathogenic | 0.358 | Stabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/Q | 0.9117 | likely_pathogenic | 0.8914 | pathogenic | -0.3 | Destabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | N |
| D/R | 0.9322 | likely_pathogenic | 0.9206 | pathogenic | 0.597 | Stabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/S | 0.4783 | ambiguous | 0.4256 | ambiguous | -0.555 | Destabilizing | 0.983 | D | 0.468 | neutral | None | None | None | None | N |
| D/T | 0.8389 | likely_pathogenic | 0.8077 | pathogenic | -0.291 | Destabilizing | 0.995 | D | 0.651 | neutral | None | None | None | None | N |
| D/V | 0.912 | likely_pathogenic | 0.8926 | pathogenic | 0.358 | Stabilizing | 0.994 | D | 0.745 | deleterious | N | 0.493209249 | None | None | N |
| D/W | 0.9941 | likely_pathogenic | 0.9916 | pathogenic | 0.621 | Stabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/Y | 0.8415 | likely_pathogenic | 0.8063 | pathogenic | 0.667 | Stabilizing | 0.576 | D | 0.419 | neutral | N | 0.496451706 | 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.