Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18140 | 54643;54644;54645 | chr2:178604269;178604268;178604267 | chr2:179468996;179468995;179468994 |
| N2AB | 16499 | 49720;49721;49722 | chr2:178604269;178604268;178604267 | chr2:179468996;179468995;179468994 |
| N2A | 15572 | 46939;46940;46941 | chr2:178604269;178604268;178604267 | chr2:179468996;179468995;179468994 |
| N2B | 9075 | 27448;27449;27450 | chr2:178604269;178604268;178604267 | chr2:179468996;179468995;179468994 |
| Novex-1 | 9200 | 27823;27824;27825 | chr2:178604269;178604268;178604267 | chr2:179468996;179468995;179468994 |
| Novex-2 | 9267 | 28024;28025;28026 | chr2:178604269;178604268;178604267 | chr2:179468996;179468995;179468994 |
| 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 | rs747236787  |
-2.324 | 0.998 | D | 0.665 | 0.425 | 0.723075696567 | gnomAD-4.0.0 | 7.13933E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.94681E-05 | 0 | 0 | 0 | 0 |
| R/Q | rs547224785 |
-0.996 | 0.978 | N | 0.467 | 0.359 | 0.365703291355 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 9.22509E-04 |
| R/Q | rs547224785 |
-0.996 | 0.978 | N | 0.467 | 0.359 | 0.365703291355 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs547224785 |
-0.996 | 0.978 | N | 0.467 | 0.359 | 0.365703291355 | gnomAD-4.0.0 | 9.02008E-06 | None | None | None | None | N | None | 9.58405E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.23015E-06 | 1.25606E-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 | 0.7755 | likely_pathogenic | 0.8548 | pathogenic | -1.923 | Destabilizing | 0.992 | D | 0.609 | neutral | None | None | None | None | N |
| R/C | 0.2419 | likely_benign | 0.3089 | benign | -1.895 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/D | 0.9874 | likely_pathogenic | 0.9936 | pathogenic | -1.183 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| R/E | 0.8414 | likely_pathogenic | 0.9106 | pathogenic | -0.968 | Destabilizing | 0.983 | D | 0.585 | neutral | None | None | None | None | N |
| R/F | 0.9099 | likely_pathogenic | 0.9429 | pathogenic | -1.04 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| R/G | 0.7973 | likely_pathogenic | 0.8654 | pathogenic | -2.248 | Highly Destabilizing | 0.998 | D | 0.665 | neutral | D | 0.523206923 | None | None | N |
| R/H | 0.2682 | likely_benign | 0.2945 | benign | -2.257 | Highly Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| R/I | 0.6498 | likely_pathogenic | 0.7558 | pathogenic | -0.975 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| R/K | 0.249 | likely_benign | 0.3186 | benign | -1.477 | Destabilizing | 0.96 | D | 0.607 | neutral | None | None | None | None | N |
| R/L | 0.6426 | likely_pathogenic | 0.7244 | pathogenic | -0.975 | Destabilizing | 0.998 | D | 0.665 | neutral | N | 0.500747802 | None | None | N |
| R/M | 0.6945 | likely_pathogenic | 0.8095 | pathogenic | -1.521 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| R/N | 0.9454 | likely_pathogenic | 0.9685 | pathogenic | -1.542 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| R/P | 0.9981 | likely_pathogenic | 0.9984 | pathogenic | -1.281 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | D | 0.535234792 | None | None | N |
| R/Q | 0.2118 | likely_benign | 0.2649 | benign | -1.259 | Destabilizing | 0.978 | D | 0.467 | neutral | N | 0.479045468 | None | None | N |
| R/S | 0.8728 | likely_pathogenic | 0.9177 | pathogenic | -2.259 | Highly Destabilizing | 0.992 | D | 0.637 | neutral | None | None | None | None | N |
| R/T | 0.7458 | likely_pathogenic | 0.8235 | pathogenic | -1.844 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| R/V | 0.6849 | likely_pathogenic | 0.793 | pathogenic | -1.281 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | N |
| R/W | 0.633 | likely_pathogenic | 0.6818 | pathogenic | -0.705 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/Y | 0.8198 | likely_pathogenic | 0.8852 | pathogenic | -0.564 | Destabilizing | 1.0 | D | 0.763 | deleterious | 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.