Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22996 | 69211;69212;69213 | chr2:178577349;178577348;178577347 | chr2:179442076;179442075;179442074 |
| N2AB | 21355 | 64288;64289;64290 | chr2:178577349;178577348;178577347 | chr2:179442076;179442075;179442074 |
| N2A | 20428 | 61507;61508;61509 | chr2:178577349;178577348;178577347 | chr2:179442076;179442075;179442074 |
| N2B | 13931 | 42016;42017;42018 | chr2:178577349;178577348;178577347 | chr2:179442076;179442075;179442074 |
| Novex-1 | 14056 | 42391;42392;42393 | chr2:178577349;178577348;178577347 | chr2:179442076;179442075;179442074 |
| Novex-2 | 14123 | 42592;42593;42594 | chr2:178577349;178577348;178577347 | chr2:179442076;179442075;179442074 |
| 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 | rs971749433  |
-1.325 | 0.989 | N | 0.576 | 0.592 | 0.758577777949 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.1197E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs971749433 |
-1.325 | 0.989 | N | 0.576 | 0.592 | 0.758577777949 | gnomAD-4.0.0 | 3.18416E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.55895E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.333 | N | 0.183 | 0.078 | 0.611273083002 | gnomAD-4.0.0 | 4.79049E-06 | None | None | None | None | N | None | 2.98954E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.3976E-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 | 0.72 | likely_pathogenic | 0.6766 | pathogenic | -1.838 | Destabilizing | 0.992 | D | 0.467 | neutral | None | None | None | None | N |
| I/C | 0.7988 | likely_pathogenic | 0.7657 | pathogenic | -1.229 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | N |
| I/D | 0.9262 | likely_pathogenic | 0.9169 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| I/E | 0.7779 | likely_pathogenic | 0.7507 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/F | 0.2509 | likely_benign | 0.2063 | benign | -1.334 | Destabilizing | 0.999 | D | 0.554 | neutral | None | None | None | None | N |
| I/G | 0.8993 | likely_pathogenic | 0.8789 | pathogenic | -2.195 | Highly Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/H | 0.7466 | likely_pathogenic | 0.7006 | pathogenic | -1.452 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/K | 0.6242 | likely_pathogenic | 0.5751 | pathogenic | -1.198 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | N | 0.518666198 | None | None | N |
| I/L | 0.1847 | likely_benign | 0.1665 | benign | -0.919 | Destabilizing | 0.889 | D | 0.317 | neutral | D | 0.522303833 | None | None | N |
| I/M | 0.1336 | likely_benign | 0.117 | benign | -0.746 | Destabilizing | 0.998 | D | 0.567 | neutral | N | 0.495229117 | None | None | N |
| I/N | 0.5567 | ambiguous | 0.5459 | ambiguous | -1.01 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| I/P | 0.9536 | likely_pathogenic | 0.9477 | pathogenic | -1.195 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| I/Q | 0.6566 | likely_pathogenic | 0.6226 | pathogenic | -1.161 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| I/R | 0.5643 | likely_pathogenic | 0.5208 | ambiguous | -0.67 | Destabilizing | 0.999 | D | 0.749 | deleterious | N | 0.521553034 | None | None | N |
| I/S | 0.6724 | likely_pathogenic | 0.6481 | pathogenic | -1.705 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| I/T | 0.5698 | likely_pathogenic | 0.5245 | ambiguous | -1.554 | Destabilizing | 0.989 | D | 0.576 | neutral | N | 0.502181331 | None | None | N |
| I/V | 0.1218 | likely_benign | 0.1058 | benign | -1.195 | Destabilizing | 0.333 | N | 0.183 | neutral | N | 0.494671727 | None | None | N |
| I/W | 0.8358 | likely_pathogenic | 0.8112 | pathogenic | -1.401 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/Y | 0.6035 | likely_pathogenic | 0.5837 | pathogenic | -1.174 | Destabilizing | 1.0 | D | 0.633 | 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.