Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9728 | 29407;29408;29409 | chr2:178706692;178706691;178706690 | chr2:179571419;179571418;179571417 |
| N2AB | 9411 | 28456;28457;28458 | chr2:178706692;178706691;178706690 | chr2:179571419;179571418;179571417 |
| N2A | 8484 | 25675;25676;25677 | chr2:178706692;178706691;178706690 | chr2:179571419;179571418;179571417 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs794729400  |
0.612 | 0.505 | None | 0.518 | 0.278 | 0.246773566709 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.12E-05 | 0 |
| N/D | rs794729400 |
0.612 | 0.505 | None | 0.518 | 0.278 | 0.246773566709 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| N/D | rs794729400 |
0.612 | 0.505 | None | 0.518 | 0.278 | 0.246773566709 | gnomAD-4.0.0 | 1.61162E-05 | None | None | None | None | I | None | 2.67037E-05 | 1.66739E-05 | None | 0 | 0 | None | 0 | 0 | 1.86526E-05 | 1.09885E-05 | 0 |
| N/S | rs374981132 |
0.064 | 0.001 | None | 0.175 | 0.11 | None | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.3E-05 | 6.2E-05 | 0 |
| N/S | rs374981132 |
0.064 | 0.001 | None | 0.175 | 0.11 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/S | rs374981132 |
0.064 | 0.001 | None | 0.175 | 0.11 | None | gnomAD-4.0.0 | 2.04544E-05 | None | None | None | None | I | None | 0 | 0 | None | 3.37906E-05 | 0 | None | 1.56211E-05 | 0 | 2.54347E-05 | 0 | 1.60102E-05 |
| N/Y | rs794729400 |
-0.124 | 0.879 | None | 0.759 | 0.473 | 0.652033478655 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| N/Y | rs794729400 |
-0.124 | 0.879 | None | 0.759 | 0.473 | 0.652033478655 | gnomAD-4.0.0 | 6.84414E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51927E-05 | None | 0 | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3838 | ambiguous | 0.283 | benign | -0.632 | Destabilizing | 0.218 | N | 0.625 | neutral | None | None | None | None | I |
| N/C | 0.6156 | likely_pathogenic | 0.5275 | ambiguous | 0.129 | Stabilizing | 0.973 | D | 0.753 | deleterious | None | None | None | None | I |
| N/D | 0.321 | likely_benign | 0.182 | benign | 0.095 | Stabilizing | 0.505 | D | 0.518 | neutral | None | None | None | None | I |
| N/E | 0.6046 | likely_pathogenic | 0.4696 | ambiguous | 0.152 | Stabilizing | 0.404 | N | 0.502 | neutral | None | None | None | None | I |
| N/F | 0.7956 | likely_pathogenic | 0.7094 | pathogenic | -0.544 | Destabilizing | 0.906 | D | 0.761 | deleterious | None | None | None | None | I |
| N/G | 0.5689 | likely_pathogenic | 0.4369 | ambiguous | -0.921 | Destabilizing | 0.218 | N | 0.518 | neutral | None | None | None | None | I |
| N/H | 0.1432 | likely_benign | 0.1156 | benign | -0.692 | Destabilizing | 0.879 | D | 0.578 | neutral | None | None | None | None | I |
| N/I | 0.3797 | ambiguous | 0.2992 | benign | 0.076 | Stabilizing | 0.782 | D | 0.758 | deleterious | None | None | None | None | I |
| N/K | 0.3418 | ambiguous | 0.2537 | benign | -0.119 | Destabilizing | 0.338 | N | 0.517 | neutral | None | None | None | None | I |
| N/L | 0.4163 | ambiguous | 0.3519 | ambiguous | 0.076 | Stabilizing | 0.575 | D | 0.641 | neutral | None | None | None | None | I |
| N/M | 0.5401 | ambiguous | 0.458 | ambiguous | 0.27 | Stabilizing | 0.991 | D | 0.741 | deleterious | None | None | None | None | I |
| N/P | 0.9452 | likely_pathogenic | 0.8832 | pathogenic | -0.131 | Destabilizing | 0.826 | D | 0.747 | deleterious | None | None | None | None | I |
| N/Q | 0.4674 | ambiguous | 0.3788 | ambiguous | -0.531 | Destabilizing | 0.826 | D | 0.577 | neutral | None | None | None | None | I |
| N/R | 0.367 | ambiguous | 0.2832 | benign | -0.15 | Destabilizing | 0.826 | D | 0.544 | neutral | None | None | None | None | I |
| N/S | 0.1165 | likely_benign | 0.0924 | benign | -0.571 | Destabilizing | 0.001 | N | 0.175 | neutral | None | None | None | None | I |
| N/T | 0.2018 | likely_benign | 0.1561 | benign | -0.335 | Destabilizing | 0.013 | N | 0.297 | neutral | None | None | None | None | I |
| N/V | 0.3268 | likely_benign | 0.2623 | benign | -0.131 | Destabilizing | 0.826 | D | 0.656 | neutral | None | None | None | None | I |
| N/W | 0.9279 | likely_pathogenic | 0.8781 | pathogenic | -0.389 | Destabilizing | 0.991 | D | 0.741 | deleterious | None | None | None | None | I |
| N/Y | 0.3515 | ambiguous | 0.2687 | benign | -0.172 | Destabilizing | 0.879 | D | 0.759 | deleterious | 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.