Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18558 | 55897;55898;55899 | chr2:178601325;178601324;178601323 | chr2:179466052;179466051;179466050 |
| N2AB | 16917 | 50974;50975;50976 | chr2:178601325;178601324;178601323 | chr2:179466052;179466051;179466050 |
| N2A | 15990 | 48193;48194;48195 | chr2:178601325;178601324;178601323 | chr2:179466052;179466051;179466050 |
| N2B | 9493 | 28702;28703;28704 | chr2:178601325;178601324;178601323 | chr2:179466052;179466051;179466050 |
| Novex-1 | 9618 | 29077;29078;29079 | chr2:178601325;178601324;178601323 | chr2:179466052;179466051;179466050 |
| Novex-2 | 9685 | 29278;29279;29280 | chr2:178601325;178601324;178601323 | chr2:179466052;179466051;179466050 |
| 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/C | rs774262905  |
-0.053 | 1.0 | N | 0.715 | 0.42 | 0.69737875697 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.64E-05 | None | 3.31E-05 | None | 0 | 8.99E-06 | 0 |
| R/C | rs774262905 |
-0.053 | 1.0 | N | 0.715 | 0.42 | 0.69737875697 | gnomAD-4.0.0 | 1.37327E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.62387E-05 | 2.33721E-05 | 0 |
| R/H | rs115867512 |
-0.789 | 1.0 | N | 0.697 | 0.328 | None | gnomAD-2.1.1 | 7.95E-05 | None | None | None | None | I | None | 2.48468E-04 | 5.71E-05 | None | 0 | 5.2E-05 | None | 3.33E-05 | None | 0 | 7.91E-05 | 2.84252E-04 |
| R/H | rs115867512 |
-0.789 | 1.0 | N | 0.697 | 0.328 | None | gnomAD-3.1.2 | 1.51314E-04 | None | None | None | None | I | None | 2.65495E-04 | 1.31268E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.32392E-04 | 0 | 4.78011E-04 |
| R/H | rs115867512 |
-0.789 | 1.0 | N | 0.697 | 0.328 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/H | rs115867512 |
-0.789 | 1.0 | N | 0.697 | 0.328 | None | gnomAD-4.0.0 | 1.1009E-04 | None | None | None | None | I | None | 2.13709E-04 | 6.70084E-05 | None | 0 | 8.97545E-05 | None | 1.56622E-05 | 0 | 1.08843E-04 | 3.32285E-05 | 3.3761E-04 |
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 | 0.5713 | likely_pathogenic | 0.6116 | pathogenic | -0.116 | Destabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | I |
| R/C | 0.2758 | likely_benign | 0.2613 | benign | -0.23 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.495006448 | None | None | I |
| R/D | 0.7858 | likely_pathogenic | 0.8122 | pathogenic | -0.045 | Destabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | I |
| R/E | 0.5485 | ambiguous | 0.6059 | pathogenic | 0.045 | Stabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| R/F | 0.7765 | likely_pathogenic | 0.7918 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| R/G | 0.4891 | ambiguous | 0.5028 | ambiguous | -0.338 | Destabilizing | 1.0 | D | 0.554 | neutral | N | 0.484227368 | None | None | I |
| R/H | 0.1657 | likely_benign | 0.1651 | benign | -1.001 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.468001423 | None | None | I |
| R/I | 0.4213 | ambiguous | 0.4387 | ambiguous | 0.44 | Stabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| R/K | 0.1696 | likely_benign | 0.1818 | benign | -0.106 | Destabilizing | 0.998 | D | 0.429 | neutral | None | None | None | None | I |
| R/L | 0.4389 | ambiguous | 0.4544 | ambiguous | 0.44 | Stabilizing | 1.0 | D | 0.554 | neutral | N | 0.471362432 | None | None | I |
| R/M | 0.5088 | ambiguous | 0.5402 | ambiguous | -0.058 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| R/N | 0.6441 | likely_pathogenic | 0.6884 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/P | 0.7421 | likely_pathogenic | 0.7257 | pathogenic | 0.275 | Stabilizing | 1.0 | D | 0.641 | neutral | N | 0.482136786 | None | None | I |
| R/Q | 0.156 | likely_benign | 0.1639 | benign | 0.026 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| R/S | 0.6348 | likely_pathogenic | 0.6572 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.618 | neutral | N | 0.429206379 | None | None | I |
| R/T | 0.4368 | ambiguous | 0.4794 | ambiguous | -0.062 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| R/V | 0.5225 | ambiguous | 0.5567 | ambiguous | 0.275 | Stabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| R/W | 0.4211 | ambiguous | 0.4199 | ambiguous | -0.331 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| R/Y | 0.5862 | likely_pathogenic | 0.6055 | pathogenic | 0.076 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | 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.