Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29568 | 88927;88928;88929 | chr2:178554645;178554644;178554643 | chr2:179419372;179419371;179419370 |
| N2AB | 27927 | 84004;84005;84006 | chr2:178554645;178554644;178554643 | chr2:179419372;179419371;179419370 |
| N2A | 27000 | 81223;81224;81225 | chr2:178554645;178554644;178554643 | chr2:179419372;179419371;179419370 |
| N2B | 20503 | 61732;61733;61734 | chr2:178554645;178554644;178554643 | chr2:179419372;179419371;179419370 |
| Novex-1 | 20628 | 62107;62108;62109 | chr2:178554645;178554644;178554643 | chr2:179419372;179419371;179419370 |
| Novex-2 | 20695 | 62308;62309;62310 | chr2:178554645;178554644;178554643 | chr2:179419372;179419371;179419370 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/D | None | None | 1.0 | N | 0.732 | 0.44 | 0.42130639912 | gnomAD-4.0.0 | 1.59104E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02371E-05 |
| H/P | None | None | 1.0 | N | 0.83 | 0.613 | 0.529060795929 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| H/Q | rs370093328  |
-1.195 | 1.0 | N | 0.704 | 0.284 | 0.430010490656 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.7688 | likely_pathogenic | 0.7417 | pathogenic | -1.31 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | N |
| H/C | 0.4133 | ambiguous | 0.373 | ambiguous | -0.399 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| H/D | 0.6453 | likely_pathogenic | 0.6099 | pathogenic | -1.235 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.486849173 | None | None | N |
| H/E | 0.8423 | likely_pathogenic | 0.8081 | pathogenic | -1.084 | Destabilizing | 0.999 | D | 0.529 | neutral | None | None | None | None | N |
| H/F | 0.7261 | likely_pathogenic | 0.7161 | pathogenic | 0.377 | Stabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| H/G | 0.5527 | ambiguous | 0.5282 | ambiguous | -1.694 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| H/I | 0.9776 | likely_pathogenic | 0.9722 | pathogenic | -0.202 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| H/K | 0.8204 | likely_pathogenic | 0.788 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| H/L | 0.8081 | likely_pathogenic | 0.7977 | pathogenic | -0.202 | Destabilizing | 1.0 | D | 0.804 | deleterious | N | 0.51474785 | None | None | N |
| H/M | 0.9492 | likely_pathogenic | 0.9393 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| H/N | 0.2488 | likely_benign | 0.2252 | benign | -1.25 | Destabilizing | 0.999 | D | 0.549 | neutral | N | 0.41800795 | None | None | N |
| H/P | 0.9864 | likely_pathogenic | 0.9849 | pathogenic | -0.558 | Destabilizing | 1.0 | D | 0.83 | deleterious | N | 0.482649411 | None | None | N |
| H/Q | 0.6747 | likely_pathogenic | 0.637 | pathogenic | -0.898 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | N | 0.503184062 | None | None | N |
| H/R | 0.4948 | ambiguous | 0.4614 | ambiguous | -1.238 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.479691127 | None | None | N |
| H/S | 0.4425 | ambiguous | 0.4048 | ambiguous | -1.291 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| H/T | 0.8299 | likely_pathogenic | 0.8008 | pathogenic | -1.041 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| H/V | 0.9518 | likely_pathogenic | 0.9416 | pathogenic | -0.558 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| H/W | 0.7293 | likely_pathogenic | 0.7239 | pathogenic | 0.764 | Stabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| H/Y | 0.2225 | likely_benign | 0.2118 | benign | 0.693 | Stabilizing | 0.999 | D | 0.586 | neutral | N | 0.455142186 | 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.