Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29465 | 88618;88619;88620 | chr2:178555066;178555065;178555064 | chr2:179419793;179419792;179419791 |
| N2AB | 27824 | 83695;83696;83697 | chr2:178555066;178555065;178555064 | chr2:179419793;179419792;179419791 |
| N2A | 26897 | 80914;80915;80916 | chr2:178555066;178555065;178555064 | chr2:179419793;179419792;179419791 |
| N2B | 20400 | 61423;61424;61425 | chr2:178555066;178555065;178555064 | chr2:179419793;179419792;179419791 |
| Novex-1 | 20525 | 61798;61799;61800 | chr2:178555066;178555065;178555064 | chr2:179419793;179419792;179419791 |
| Novex-2 | 20592 | 61999;62000;62001 | chr2:178555066;178555065;178555064 | chr2:179419793;179419792;179419791 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs146181116  |
-0.835 | 0.988 | D | 0.349 | 0.331 | None | gnomAD-2.1.1 | 3.13962E-03 | None | None | None | None | I | None | 5.78799E-04 | 1.2732E-03 | None | 2.03331E-03 | 0 | None | 1.96117E-04 | None | 6.31545E-03 | 4.7872E-03 | 3.23306E-03 |
| S/F | rs146181116 |
-0.835 | 0.988 | D | 0.349 | 0.331 | None | gnomAD-3.1.2 | 3.25363E-03 | None | None | None | None | I | None | 7.72201E-04 | 1.44092E-03 | 0 | 1.15274E-03 | 0 | None | 5.18672E-03 | 0 | 5.55735E-03 | 2.07211E-04 | 1.43541E-03 |
| S/F | rs146181116 |
-0.835 | 0.988 | D | 0.349 | 0.331 | None | 1000 genomes | 1.79712E-03 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 7E-03 | None | None | None | 1E-03 | None |
| S/F | rs146181116 |
-0.835 | 0.988 | D | 0.349 | 0.331 | None | gnomAD-4.0.0 | 3.75516E-03 | None | None | None | None | I | None | 5.9968E-04 | 1.36648E-03 | None | 1.92555E-03 | 0 | None | 6.75E-03 | 1.65071E-04 | 4.46768E-03 | 2.08626E-04 | 2.44925E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0837 | likely_benign | 0.0789 | benign | -0.133 | Destabilizing | 0.675 | D | 0.152 | neutral | N | 0.467893345 | None | None | I |
| S/C | 0.1092 | likely_benign | 0.1073 | benign | -0.552 | Destabilizing | 0.999 | D | 0.286 | neutral | N | 0.491065289 | None | None | I |
| S/D | 0.5315 | ambiguous | 0.5224 | ambiguous | 0.005 | Stabilizing | 0.969 | D | 0.253 | neutral | None | None | None | None | I |
| S/E | 0.545 | ambiguous | 0.5444 | ambiguous | -0.089 | Destabilizing | 0.969 | D | 0.175 | neutral | None | None | None | None | I |
| S/F | 0.1657 | likely_benign | 0.154 | benign | -0.926 | Destabilizing | 0.988 | D | 0.349 | neutral | D | 0.5282698 | None | None | I |
| S/G | 0.1162 | likely_benign | 0.1159 | benign | -0.16 | Destabilizing | 0.969 | D | 0.17 | neutral | None | None | None | None | I |
| S/H | 0.3104 | likely_benign | 0.2992 | benign | -0.376 | Destabilizing | 0.999 | D | 0.287 | neutral | None | None | None | None | I |
| S/I | 0.1496 | likely_benign | 0.1462 | benign | -0.189 | Destabilizing | 0.17 | N | 0.201 | neutral | None | None | None | None | I |
| S/K | 0.5911 | likely_pathogenic | 0.5635 | ambiguous | -0.371 | Destabilizing | 0.969 | D | 0.175 | neutral | None | None | None | None | I |
| S/L | 0.0918 | likely_benign | 0.0887 | benign | -0.189 | Destabilizing | 0.759 | D | 0.284 | neutral | None | None | None | None | I |
| S/M | 0.1867 | likely_benign | 0.1866 | benign | -0.36 | Destabilizing | 0.991 | D | 0.287 | neutral | None | None | None | None | I |
| S/N | 0.1876 | likely_benign | 0.1831 | benign | -0.234 | Destabilizing | 0.969 | D | 0.283 | neutral | None | None | None | None | I |
| S/P | 0.865 | likely_pathogenic | 0.8771 | pathogenic | -0.148 | Destabilizing | 0.996 | D | 0.317 | neutral | N | 0.49055831 | None | None | I |
| S/Q | 0.4506 | ambiguous | 0.4485 | ambiguous | -0.39 | Destabilizing | 0.997 | D | 0.307 | neutral | None | None | None | None | I |
| S/R | 0.4388 | ambiguous | 0.417 | ambiguous | -0.129 | Destabilizing | 0.991 | D | 0.317 | neutral | None | None | None | None | I |
| S/T | 0.0771 | likely_benign | 0.074 | benign | -0.321 | Destabilizing | 0.061 | N | 0.075 | neutral | N | 0.424737213 | None | None | I |
| S/V | 0.1755 | likely_benign | 0.1749 | benign | -0.148 | Destabilizing | 0.17 | N | 0.187 | neutral | None | None | None | None | I |
| S/W | 0.2707 | likely_benign | 0.2652 | benign | -1.056 | Destabilizing | 0.999 | D | 0.381 | neutral | None | None | None | None | I |
| S/Y | 0.1671 | likely_benign | 0.1557 | benign | -0.713 | Destabilizing | 0.996 | D | 0.341 | neutral | N | 0.517495446 | 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.