Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16167 | 48724;48725;48726 | chr2:178615446;178615445;178615444 | chr2:179480173;179480172;179480171 |
| N2AB | 14526 | 43801;43802;43803 | chr2:178615446;178615445;178615444 | chr2:179480173;179480172;179480171 |
| N2A | 13599 | 41020;41021;41022 | chr2:178615446;178615445;178615444 | chr2:179480173;179480172;179480171 |
| N2B | 7102 | 21529;21530;21531 | chr2:178615446;178615445;178615444 | chr2:179480173;179480172;179480171 |
| Novex-1 | 7227 | 21904;21905;21906 | chr2:178615446;178615445;178615444 | chr2:179480173;179480172;179480171 |
| Novex-2 | 7294 | 22105;22106;22107 | chr2:178615446;178615445;178615444 | chr2:179480173;179480172;179480171 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1312425985  |
-1.315 | 0.653 | N | 0.259 | 0.2 | 0.348324211639 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/G | rs1312425985 |
-1.315 | 0.653 | N | 0.259 | 0.2 | 0.348324211639 | gnomAD-4.0.0 | 3.42388E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.50047E-06 | 0 | 0 |
| R/Q | rs778774812 |
-0.262 | 0.91 | N | 0.244 | 0.156 | 0.190952846119 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/Q | rs778774812 |
-0.262 | 0.91 | N | 0.244 | 0.156 | 0.190952846119 | gnomAD-4.0.0 | 7.53244E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00085E-06 | 1.16101E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5903 | likely_pathogenic | 0.5851 | pathogenic | -1.856 | Destabilizing | 0.495 | N | 0.252 | neutral | None | None | None | None | N |
| R/C | 0.2781 | likely_benign | 0.2937 | benign | -1.81 | Destabilizing | 0.995 | D | 0.181 | neutral | None | None | None | None | N |
| R/D | 0.9403 | likely_pathogenic | 0.9282 | pathogenic | -0.793 | Destabilizing | 0.828 | D | 0.315 | neutral | None | None | None | None | N |
| R/E | 0.6987 | likely_pathogenic | 0.6687 | pathogenic | -0.58 | Destabilizing | 0.495 | N | 0.272 | neutral | None | None | None | None | N |
| R/F | 0.8665 | likely_pathogenic | 0.8454 | pathogenic | -1.302 | Destabilizing | 0.981 | D | 0.22 | neutral | None | None | None | None | N |
| R/G | 0.5773 | likely_pathogenic | 0.5605 | ambiguous | -2.231 | Highly Destabilizing | 0.653 | D | 0.259 | neutral | N | 0.46057859 | None | None | N |
| R/H | 0.2507 | likely_benign | 0.2414 | benign | -2.167 | Highly Destabilizing | 0.981 | D | 0.294 | neutral | None | None | None | None | N |
| R/I | 0.4493 | ambiguous | 0.4341 | ambiguous | -0.782 | Destabilizing | 0.944 | D | 0.294 | neutral | None | None | None | None | N |
| R/K | 0.1423 | likely_benign | 0.1359 | benign | -1.285 | Destabilizing | 0.004 | N | 0.09 | neutral | None | None | None | None | N |
| R/L | 0.5525 | ambiguous | 0.5159 | ambiguous | -0.782 | Destabilizing | 0.653 | D | 0.299 | neutral | N | 0.426981366 | None | None | N |
| R/M | 0.5726 | likely_pathogenic | 0.5342 | ambiguous | -1.158 | Destabilizing | 0.981 | D | 0.239 | neutral | None | None | None | None | N |
| R/N | 0.8494 | likely_pathogenic | 0.8354 | pathogenic | -1.24 | Destabilizing | 0.828 | D | 0.229 | neutral | None | None | None | None | N |
| R/P | 0.6073 | likely_pathogenic | 0.6154 | pathogenic | -1.125 | Destabilizing | 0.002 | N | 0.136 | neutral | N | 0.392398847 | None | None | N |
| R/Q | 0.1837 | likely_benign | 0.1772 | benign | -1.206 | Destabilizing | 0.91 | D | 0.244 | neutral | N | 0.371492482 | None | None | N |
| R/S | 0.7444 | likely_pathogenic | 0.7357 | pathogenic | -2.215 | Highly Destabilizing | 0.495 | N | 0.267 | neutral | None | None | None | None | N |
| R/T | 0.4188 | ambiguous | 0.4095 | ambiguous | -1.768 | Destabilizing | 0.495 | N | 0.297 | neutral | None | None | None | None | N |
| R/V | 0.4789 | ambiguous | 0.4645 | ambiguous | -1.125 | Destabilizing | 0.828 | D | 0.333 | neutral | None | None | None | None | N |
| R/W | 0.5778 | likely_pathogenic | 0.5379 | ambiguous | -0.772 | Destabilizing | 0.995 | D | 0.209 | neutral | None | None | None | None | N |
| R/Y | 0.7499 | likely_pathogenic | 0.7278 | pathogenic | -0.597 | Destabilizing | 0.981 | D | 0.229 | 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.