Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24331 | 73216;73217;73218 | chr2:178573141;178573140;178573139 | chr2:179437868;179437867;179437866 |
| N2AB | 22690 | 68293;68294;68295 | chr2:178573141;178573140;178573139 | chr2:179437868;179437867;179437866 |
| N2A | 21763 | 65512;65513;65514 | chr2:178573141;178573140;178573139 | chr2:179437868;179437867;179437866 |
| N2B | 15266 | 46021;46022;46023 | chr2:178573141;178573140;178573139 | chr2:179437868;179437867;179437866 |
| Novex-1 | 15391 | 46396;46397;46398 | chr2:178573141;178573140;178573139 | chr2:179437868;179437867;179437866 |
| Novex-2 | 15458 | 46597;46598;46599 | chr2:178573141;178573140;178573139 | chr2:179437868;179437867;179437866 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs376591763  |
-0.561 | 1.0 | N | 0.777 | 0.348 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| R/C | rs376591763 |
-0.561 | 1.0 | N | 0.777 | 0.348 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs376591763 |
-0.561 | 1.0 | N | 0.777 | 0.348 | None | gnomAD-4.0.0 | 3.96748E-05 | None | None | None | None | N | None | 2.6713E-05 | 3.33622E-05 | None | 0 | 0 | None | 0 | 0 | 4.49337E-05 | 3.2954E-05 | 6.40697E-05 |
| R/H | rs755174224 |
-1.24 | 0.385 | N | 0.318 | 0.205 | None | gnomAD-2.1.1 | 1.32321E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.75384E-03 | None | 0 | None | 0 | 2.35E-05 | 0 |
| R/H | rs755174224 |
-1.24 | 0.385 | N | 0.318 | 0.205 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.1646E-03 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs755174224 |
-1.24 | 0.385 | N | 0.318 | 0.205 | None | gnomAD-4.0.0 | 2.47967E-05 | None | None | None | None | N | None | 1.33547E-05 | 1.66811E-05 | None | 0 | 5.58684E-04 | None | 0 | 0 | 1.01737E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7658 | likely_pathogenic | 0.8296 | pathogenic | -0.831 | Destabilizing | 0.953 | D | 0.643 | neutral | None | None | None | None | N |
| R/C | 0.3094 | likely_benign | 0.4014 | ambiguous | -0.916 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.474068264 | None | None | N |
| R/D | 0.934 | likely_pathogenic | 0.9493 | pathogenic | -0.037 | Destabilizing | 0.986 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/E | 0.711 | likely_pathogenic | 0.7644 | pathogenic | 0.131 | Stabilizing | 0.953 | D | 0.573 | neutral | None | None | None | None | N |
| R/F | 0.7896 | likely_pathogenic | 0.8505 | pathogenic | -0.453 | Destabilizing | 0.993 | D | 0.777 | deleterious | None | None | None | None | N |
| R/G | 0.7285 | likely_pathogenic | 0.8032 | pathogenic | -1.178 | Destabilizing | 0.975 | D | 0.662 | neutral | N | 0.471168202 | None | None | N |
| R/H | 0.1748 | likely_benign | 0.215 | benign | -1.342 | Destabilizing | 0.385 | N | 0.318 | neutral | N | 0.46993828 | None | None | N |
| R/I | 0.5377 | ambiguous | 0.6174 | pathogenic | 0.115 | Stabilizing | 0.993 | D | 0.78 | deleterious | None | None | None | None | N |
| R/K | 0.1413 | likely_benign | 0.1818 | benign | -0.731 | Destabilizing | 0.893 | D | 0.543 | neutral | None | None | None | None | N |
| R/L | 0.5388 | ambiguous | 0.6114 | pathogenic | 0.115 | Stabilizing | 0.993 | D | 0.667 | neutral | N | 0.507419233 | None | None | N |
| R/M | 0.5757 | likely_pathogenic | 0.652 | pathogenic | -0.419 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | None | None | None | None | N |
| R/N | 0.8603 | likely_pathogenic | 0.9019 | pathogenic | -0.471 | Destabilizing | 0.953 | D | 0.609 | neutral | None | None | None | None | N |
| R/P | 0.9807 | likely_pathogenic | 0.9835 | pathogenic | -0.18 | Destabilizing | 0.999 | D | 0.773 | deleterious | N | 0.506162171 | None | None | N |
| R/Q | 0.2027 | likely_benign | 0.245 | benign | -0.491 | Destabilizing | 0.986 | D | 0.624 | neutral | None | None | None | None | N |
| R/S | 0.832 | likely_pathogenic | 0.8835 | pathogenic | -1.247 | Destabilizing | 0.975 | D | 0.703 | prob.neutral | N | 0.472071722 | None | None | N |
| R/T | 0.6111 | likely_pathogenic | 0.6946 | pathogenic | -0.871 | Destabilizing | 0.993 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/V | 0.5787 | likely_pathogenic | 0.6596 | pathogenic | -0.18 | Destabilizing | 0.993 | D | 0.785 | deleterious | None | None | None | None | N |
| R/W | 0.4017 | ambiguous | 0.4449 | ambiguous | -0.09 | Destabilizing | 0.999 | D | 0.758 | deleterious | None | None | None | None | N |
| R/Y | 0.6303 | likely_pathogenic | 0.7022 | pathogenic | 0.171 | Stabilizing | 0.986 | D | 0.783 | 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.