Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15849 | 47770;47771;47772 | chr2:178617806;178617805;178617804 | chr2:179482533;179482532;179482531 |
| N2AB | 14208 | 42847;42848;42849 | chr2:178617806;178617805;178617804 | chr2:179482533;179482532;179482531 |
| N2A | 13281 | 40066;40067;40068 | chr2:178617806;178617805;178617804 | chr2:179482533;179482532;179482531 |
| N2B | 6784 | 20575;20576;20577 | chr2:178617806;178617805;178617804 | chr2:179482533;179482532;179482531 |
| Novex-1 | 6909 | 20950;20951;20952 | chr2:178617806;178617805;178617804 | chr2:179482533;179482532;179482531 |
| Novex-2 | 6976 | 21151;21152;21153 | chr2:178617806;178617805;178617804 | chr2:179482533;179482532;179482531 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.255 | N | 0.321 | 0.124 | 0.356281029322 | gnomAD-4.0.0 | 1.36954E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80007E-06 | 0 | 0 |
| P/R | rs772636177  |
0.203 | 0.001 | N | 0.135 | 0.146 | 0.235664433957 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| P/R | rs772636177 |
0.203 | 0.001 | N | 0.135 | 0.146 | 0.235664433957 | gnomAD-4.0.0 | 2.73908E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73792E-04 | 9.00035E-07 | 0 | 3.31774E-05 |
| P/T | rs146181477 |
-0.493 | 0.255 | N | 0.215 | 0.152 | None | gnomAD-2.1.1 | 3.41504E-03 | None | None | None | None | N | None | 1.24234E-04 | 7.6561E-04 | None | 1.06693E-03 | 0 | None | 2.17732E-02 | None | 4E-05 | 1.75951E-03 | 2.95775E-03 |
| P/T | rs146181477 |
-0.493 | 0.255 | N | 0.215 | 0.152 | None | gnomAD-3.1.2 | 1.75827E-03 | None | None | None | None | N | None | 1.69123E-04 | 1.70828E-03 | 0 | 8.66051E-04 | 0 | None | 0 | 0 | 1.67904E-03 | 2.36123E-02 | 1.43816E-03 |
| P/T | rs146181477 |
-0.493 | 0.255 | N | 0.215 | 0.152 | None | 1000 genomes | 5.99042E-03 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 2.76E-02 | None |
| P/T | rs146181477 |
-0.493 | 0.255 | N | 0.215 | 0.152 | None | gnomAD-4.0.0 | 2.18253E-03 | None | None | None | None | N | None | 2.40359E-04 | 9.51681E-04 | None | 8.45966E-04 | 4.47748E-05 | None | 6.2498E-05 | 4.1336E-03 | 1.09078E-03 | 2.12581E-02 | 2.67663E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0672 | likely_benign | 0.0752 | benign | -0.566 | Destabilizing | 0.255 | N | 0.245 | neutral | N | 0.461154732 | None | None | N |
| P/C | 0.4627 | ambiguous | 0.4477 | ambiguous | -0.689 | Destabilizing | 0.989 | D | 0.339 | neutral | None | None | None | None | N |
| P/D | 0.2206 | likely_benign | 0.2364 | benign | -0.028 | Destabilizing | 0.185 | N | 0.239 | neutral | None | None | None | None | N |
| P/E | 0.1591 | likely_benign | 0.1822 | benign | -0.093 | Destabilizing | 0.09 | N | 0.244 | neutral | None | None | None | None | N |
| P/F | 0.4696 | ambiguous | 0.4794 | ambiguous | -0.545 | Destabilizing | 0.887 | D | 0.485 | neutral | None | None | None | None | N |
| P/G | 0.2061 | likely_benign | 0.2091 | benign | -0.752 | Destabilizing | 0.312 | N | 0.249 | neutral | None | None | None | None | N |
| P/H | 0.1415 | likely_benign | 0.1542 | benign | -0.177 | Destabilizing | 0.003 | N | 0.265 | neutral | N | 0.469913051 | None | None | N |
| P/I | 0.2689 | likely_benign | 0.2905 | benign | -0.207 | Destabilizing | 0.887 | D | 0.573 | neutral | None | None | None | None | N |
| P/K | 0.1739 | likely_benign | 0.185 | benign | -0.436 | Destabilizing | 0.09 | N | 0.246 | neutral | None | None | None | None | N |
| P/L | 0.1211 | likely_benign | 0.1288 | benign | -0.207 | Destabilizing | 0.255 | N | 0.321 | neutral | N | 0.46040591 | None | None | N |
| P/M | 0.2891 | likely_benign | 0.31 | benign | -0.407 | Destabilizing | 0.96 | D | 0.375 | neutral | None | None | None | None | N |
| P/N | 0.1725 | likely_benign | 0.1891 | benign | -0.264 | Destabilizing | 0.002 | N | 0.127 | neutral | None | None | None | None | N |
| P/Q | 0.0967 | likely_benign | 0.1109 | benign | -0.415 | Destabilizing | 0.018 | N | 0.073 | neutral | None | None | None | None | N |
| P/R | 0.1104 | likely_benign | 0.123 | benign | 0.011 | Stabilizing | 0.001 | N | 0.135 | neutral | N | 0.440653517 | None | None | N |
| P/S | 0.088 | likely_benign | 0.0969 | benign | -0.72 | Destabilizing | 0.255 | N | 0.247 | neutral | N | 0.467874186 | None | None | N |
| P/T | 0.0876 | likely_benign | 0.097 | benign | -0.669 | Destabilizing | 0.255 | N | 0.215 | neutral | N | 0.464215685 | None | None | N |
| P/V | 0.171 | likely_benign | 0.1865 | benign | -0.291 | Destabilizing | 0.691 | D | 0.448 | neutral | None | None | None | None | N |
| P/W | 0.6071 | likely_pathogenic | 0.6304 | pathogenic | -0.642 | Destabilizing | 0.989 | D | 0.367 | neutral | None | None | None | None | N |
| P/Y | 0.3617 | ambiguous | 0.3815 | ambiguous | -0.346 | Destabilizing | 0.524 | D | 0.569 | 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.