Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31740 | 95443;95444;95445 | chr2:178546018;178546017;178546016 | chr2:179410745;179410744;179410743 |
| N2AB | 30099 | 90520;90521;90522 | chr2:178546018;178546017;178546016 | chr2:179410745;179410744;179410743 |
| N2A | 29172 | 87739;87740;87741 | chr2:178546018;178546017;178546016 | chr2:179410745;179410744;179410743 |
| N2B | 22675 | 68248;68249;68250 | chr2:178546018;178546017;178546016 | chr2:179410745;179410744;179410743 |
| Novex-1 | 22800 | 68623;68624;68625 | chr2:178546018;178546017;178546016 | chr2:179410745;179410744;179410743 |
| Novex-2 | 22867 | 68824;68825;68826 | chr2:178546018;178546017;178546016 | chr2:179410745;179410744;179410743 |
| 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/T | rs200781956  |
-2.375 | 0.062 | D | 0.711 | 0.473 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 1.29199E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs200781956 |
-2.375 | 0.062 | D | 0.711 | 0.473 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs200781956 |
-2.375 | 0.062 | D | 0.711 | 0.473 | None | gnomAD-4.0.0 | 6.57186E-06 | None | None | None | None | I | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | None | N | 0.128 | 0.121 | 0.415055319159 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.9212 | likely_pathogenic | 0.9524 | pathogenic | -2.291 | Highly Destabilizing | 0.035 | N | 0.556 | neutral | None | None | None | None | I |
| I/C | 0.9256 | likely_pathogenic | 0.9553 | pathogenic | -1.338 | Destabilizing | 0.824 | D | 0.705 | prob.neutral | None | None | None | None | I |
| I/D | 0.9929 | likely_pathogenic | 0.9956 | pathogenic | -2.142 | Highly Destabilizing | 0.555 | D | 0.791 | deleterious | None | None | None | None | I |
| I/E | 0.9833 | likely_pathogenic | 0.989 | pathogenic | -2.076 | Highly Destabilizing | 0.555 | D | 0.818 | deleterious | None | None | None | None | I |
| I/F | 0.8138 | likely_pathogenic | 0.8823 | pathogenic | -1.553 | Destabilizing | 0.188 | N | 0.703 | prob.neutral | D | 0.545439008 | None | None | I |
| I/G | 0.9821 | likely_pathogenic | 0.9889 | pathogenic | -2.697 | Highly Destabilizing | 0.38 | N | 0.815 | deleterious | None | None | None | None | I |
| I/H | 0.9837 | likely_pathogenic | 0.9915 | pathogenic | -1.932 | Destabilizing | 0.935 | D | 0.768 | deleterious | None | None | None | None | I |
| I/K | 0.96 | likely_pathogenic | 0.972 | pathogenic | -1.758 | Destabilizing | 0.38 | N | 0.818 | deleterious | None | None | None | None | I |
| I/L | 0.2915 | likely_benign | 0.3865 | ambiguous | -1.192 | Destabilizing | None | N | 0.165 | neutral | N | 0.497367214 | None | None | I |
| I/M | 0.3439 | ambiguous | 0.4476 | ambiguous | -0.826 | Destabilizing | 0.004 | N | 0.381 | neutral | D | 0.541390538 | None | None | I |
| I/N | 0.8797 | likely_pathogenic | 0.9231 | pathogenic | -1.641 | Destabilizing | 0.484 | N | 0.796 | deleterious | D | 0.560508751 | None | None | I |
| I/P | 0.9179 | likely_pathogenic | 0.9347 | pathogenic | -1.532 | Destabilizing | 0.791 | D | 0.793 | deleterious | None | None | None | None | I |
| I/Q | 0.9739 | likely_pathogenic | 0.9833 | pathogenic | -1.77 | Destabilizing | 0.38 | N | 0.8 | deleterious | None | None | None | None | I |
| I/R | 0.9561 | likely_pathogenic | 0.97 | pathogenic | -1.116 | Destabilizing | 0.38 | N | 0.796 | deleterious | None | None | None | None | I |
| I/S | 0.9425 | likely_pathogenic | 0.9663 | pathogenic | -2.266 | Highly Destabilizing | 0.117 | N | 0.789 | deleterious | D | 0.548227393 | None | None | I |
| I/T | 0.8765 | likely_pathogenic | 0.9222 | pathogenic | -2.082 | Highly Destabilizing | 0.062 | N | 0.711 | prob.delet. | D | 0.527654376 | None | None | I |
| I/V | 0.1003 | likely_benign | 0.1356 | benign | -1.532 | Destabilizing | None | N | 0.128 | neutral | N | 0.475117601 | None | None | I |
| I/W | 0.9918 | likely_pathogenic | 0.995 | pathogenic | -1.734 | Destabilizing | 0.935 | D | 0.767 | deleterious | None | None | None | None | I |
| I/Y | 0.9526 | likely_pathogenic | 0.9715 | pathogenic | -1.54 | Destabilizing | 0.555 | D | 0.732 | prob.delet. | 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.