Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24680 | 74263;74264;74265 | chr2:178572094;178572093;178572092 | chr2:179436821;179436820;179436819 |
| N2AB | 23039 | 69340;69341;69342 | chr2:178572094;178572093;178572092 | chr2:179436821;179436820;179436819 |
| N2A | 22112 | 66559;66560;66561 | chr2:178572094;178572093;178572092 | chr2:179436821;179436820;179436819 |
| N2B | 15615 | 47068;47069;47070 | chr2:178572094;178572093;178572092 | chr2:179436821;179436820;179436819 |
| Novex-1 | 15740 | 47443;47444;47445 | chr2:178572094;178572093;178572092 | chr2:179436821;179436820;179436819 |
| Novex-2 | 15807 | 47644;47645;47646 | chr2:178572094;178572093;178572092 | chr2:179436821;179436820;179436819 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs1381899333  |
None | 0.981 | N | 0.341 | 0.223 | 0.611199080189 | 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 |
| I/F | rs1381899333 |
None | 0.981 | N | 0.341 | 0.223 | 0.611199080189 | gnomAD-4.0.0 | 3.0451E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61493E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2665 | likely_benign | 0.2865 | benign | -1.082 | Destabilizing | 0.762 | D | 0.355 | neutral | None | None | None | None | N |
| I/C | 0.5784 | likely_pathogenic | 0.6059 | pathogenic | -0.856 | Destabilizing | 0.998 | D | 0.363 | neutral | None | None | None | None | N |
| I/D | 0.6656 | likely_pathogenic | 0.6722 | pathogenic | -0.313 | Destabilizing | 0.94 | D | 0.389 | neutral | None | None | None | None | N |
| I/E | 0.5031 | ambiguous | 0.5077 | ambiguous | -0.336 | Destabilizing | 0.921 | D | 0.391 | neutral | None | None | None | None | N |
| I/F | 0.1769 | likely_benign | 0.1674 | benign | -0.747 | Destabilizing | 0.981 | D | 0.341 | neutral | N | 0.462761592 | None | None | N |
| I/G | 0.5126 | ambiguous | 0.5279 | ambiguous | -1.338 | Destabilizing | 0.94 | D | 0.389 | neutral | None | None | None | None | N |
| I/H | 0.3241 | likely_benign | 0.3392 | benign | -0.387 | Destabilizing | 0.996 | D | 0.403 | neutral | None | None | None | None | N |
| I/K | 0.2635 | likely_benign | 0.2785 | benign | -0.623 | Destabilizing | 0.186 | N | 0.393 | neutral | None | None | None | None | N |
| I/L | 0.091 | likely_benign | 0.0882 | benign | -0.488 | Destabilizing | 0.03 | N | 0.219 | neutral | N | 0.439652659 | None | None | N |
| I/M | 0.1007 | likely_benign | 0.0983 | benign | -0.58 | Destabilizing | 0.938 | D | 0.365 | neutral | N | 0.477037611 | None | None | N |
| I/N | 0.1686 | likely_benign | 0.1799 | benign | -0.519 | Destabilizing | 0.977 | D | 0.385 | neutral | N | 0.417007873 | None | None | N |
| I/P | 0.7734 | likely_pathogenic | 0.7586 | pathogenic | -0.654 | Destabilizing | 0.994 | D | 0.409 | neutral | None | None | None | None | N |
| I/Q | 0.2523 | likely_benign | 0.2748 | benign | -0.665 | Destabilizing | 0.986 | D | 0.421 | neutral | None | None | None | None | N |
| I/R | 0.2182 | likely_benign | 0.2271 | benign | -0.063 | Destabilizing | 0.956 | D | 0.419 | neutral | None | None | None | None | N |
| I/S | 0.175 | likely_benign | 0.1946 | benign | -1.098 | Destabilizing | 0.745 | D | 0.357 | neutral | N | 0.374371816 | None | None | N |
| I/T | 0.1466 | likely_benign | 0.169 | benign | -0.995 | Destabilizing | 0.003 | N | 0.107 | neutral | N | 0.36757913 | None | None | N |
| I/V | 0.0875 | likely_benign | 0.0903 | benign | -0.654 | Destabilizing | 0.039 | N | 0.225 | neutral | N | 0.427608868 | None | None | N |
| I/W | 0.7778 | likely_pathogenic | 0.7651 | pathogenic | -0.757 | Destabilizing | 0.999 | D | 0.447 | neutral | None | None | None | None | N |
| I/Y | 0.4603 | ambiguous | 0.4698 | ambiguous | -0.532 | Destabilizing | 0.887 | D | 0.367 | neutral | 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.