Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21790 | 65593;65594;65595 | chr2:178583814;178583813;178583812 | chr2:179448541;179448540;179448539 |
| N2AB | 20149 | 60670;60671;60672 | chr2:178583814;178583813;178583812 | chr2:179448541;179448540;179448539 |
| N2A | 19222 | 57889;57890;57891 | chr2:178583814;178583813;178583812 | chr2:179448541;179448540;179448539 |
| N2B | 12725 | 38398;38399;38400 | chr2:178583814;178583813;178583812 | chr2:179448541;179448540;179448539 |
| Novex-1 | 12850 | 38773;38774;38775 | chr2:178583814;178583813;178583812 | chr2:179448541;179448540;179448539 |
| Novex-2 | 12917 | 38974;38975;38976 | chr2:178583814;178583813;178583812 | chr2:179448541;179448540;179448539 |
| 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/M | rs764130758  |
None | 0.901 | N | 0.546 | 0.28 | 0.462721901306 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.69722E-04 |
| I/M | rs764130758 |
None | 0.901 | N | 0.546 | 0.28 | 0.462721901306 | gnomAD-4.0.0 | 1.60047E-06 | None | None | None | None | I | None | 5.6773E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs727503580 |
-1.644 | 0.034 | N | 0.235 | 0.274 | 0.501559347837 | gnomAD-2.1.1 | 1.24E-05 | None | None | None | None | I | None | 1.33351E-04 | 0 | None | 0 | 0 | None | 3.37E-05 | None | 0 | 0 | 0 |
| I/T | rs727503580 |
-1.644 | 0.034 | N | 0.235 | 0.274 | 0.501559347837 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs727503580 |
-1.644 | 0.034 | N | 0.235 | 0.274 | 0.501559347837 | gnomAD-4.0.0 | 1.1584E-05 | None | None | None | None | I | None | 8.46711E-05 | 0 | None | 0 | 4.89309E-05 | None | 0 | 0 | 2.40233E-06 | 1.3541E-05 | 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 | 0.2797 | likely_benign | 0.1907 | benign | -1.459 | Destabilizing | 0.415 | N | 0.448 | neutral | None | None | None | None | I |
| I/C | 0.8247 | likely_pathogenic | 0.7226 | pathogenic | -0.907 | Destabilizing | 0.996 | D | 0.607 | neutral | None | None | None | None | I |
| I/D | 0.9362 | likely_pathogenic | 0.8799 | pathogenic | -0.862 | Destabilizing | 0.961 | D | 0.689 | prob.neutral | None | None | None | None | I |
| I/E | 0.8479 | likely_pathogenic | 0.7596 | pathogenic | -0.904 | Destabilizing | 0.961 | D | 0.679 | prob.neutral | None | None | None | None | I |
| I/F | 0.3264 | likely_benign | 0.2509 | benign | -1.18 | Destabilizing | 0.901 | D | 0.536 | neutral | N | 0.516902721 | None | None | I |
| I/G | 0.8054 | likely_pathogenic | 0.666 | pathogenic | -1.728 | Destabilizing | 0.961 | D | 0.631 | neutral | None | None | None | None | I |
| I/H | 0.7882 | likely_pathogenic | 0.6785 | pathogenic | -0.92 | Destabilizing | 0.996 | D | 0.734 | prob.delet. | None | None | None | None | I |
| I/K | 0.7228 | likely_pathogenic | 0.6071 | pathogenic | -0.855 | Destabilizing | 0.961 | D | 0.687 | prob.neutral | None | None | None | None | I |
| I/L | 0.1673 | likely_benign | 0.1373 | benign | -0.822 | Destabilizing | 0.19 | N | 0.27 | neutral | N | 0.468666057 | None | None | I |
| I/M | 0.1504 | likely_benign | 0.1261 | benign | -0.597 | Destabilizing | 0.901 | D | 0.546 | neutral | N | 0.475483388 | None | None | I |
| I/N | 0.6269 | likely_pathogenic | 0.4803 | ambiguous | -0.613 | Destabilizing | 0.949 | D | 0.709 | prob.delet. | N | 0.47446943 | None | None | I |
| I/P | 0.8911 | likely_pathogenic | 0.8301 | pathogenic | -1.002 | Destabilizing | 0.987 | D | 0.705 | prob.neutral | None | None | None | None | I |
| I/Q | 0.7099 | likely_pathogenic | 0.5868 | pathogenic | -0.873 | Destabilizing | 0.987 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/R | 0.5827 | likely_pathogenic | 0.4611 | ambiguous | -0.23 | Destabilizing | 0.961 | D | 0.716 | prob.delet. | None | None | None | None | I |
| I/S | 0.3727 | ambiguous | 0.2703 | benign | -1.208 | Destabilizing | 0.565 | D | 0.584 | neutral | N | 0.495505942 | None | None | I |
| I/T | 0.0954 | likely_benign | 0.0789 | benign | -1.141 | Destabilizing | 0.034 | N | 0.235 | neutral | N | 0.443324895 | None | None | I |
| I/V | 0.0944 | likely_benign | 0.0722 | benign | -1.002 | Destabilizing | 0.003 | N | 0.119 | neutral | N | 0.497834171 | None | None | I |
| I/W | 0.8812 | likely_pathogenic | 0.8445 | pathogenic | -1.176 | Destabilizing | 0.996 | D | 0.789 | deleterious | None | None | None | None | I |
| I/Y | 0.7913 | likely_pathogenic | 0.714 | pathogenic | -0.949 | Destabilizing | 0.961 | D | 0.617 | 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.