Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35294 | 106105;106106;106107 | chr2:178530735;178530734;178530733 | chr2:179395462;179395461;179395460 |
| N2AB | 33653 | 101182;101183;101184 | chr2:178530735;178530734;178530733 | chr2:179395462;179395461;179395460 |
| N2A | 32726 | 98401;98402;98403 | chr2:178530735;178530734;178530733 | chr2:179395462;179395461;179395460 |
| N2B | 26229 | 78910;78911;78912 | chr2:178530735;178530734;178530733 | chr2:179395462;179395461;179395460 |
| Novex-1 | 26354 | 79285;79286;79287 | chr2:178530735;178530734;178530733 | chr2:179395462;179395461;179395460 |
| Novex-2 | 26421 | 79486;79487;79488 | chr2:178530735;178530734;178530733 | chr2:179395462;179395461;179395460 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs569210689  |
None | 0.446 | N | 0.559 | 0.088 | 0.152612264143 | gnomAD-4.0.0 | 3.42075E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69822E-06 | 0 | 3.31268E-05 |
| A/T | rs879080442 |
-0.866 | 0.284 | N | 0.556 | 0.103 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs879080442 |
-0.866 | 0.284 | N | 0.556 | 0.103 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs879080442 |
-0.866 | 0.284 | N | 0.556 | 0.103 | None | gnomAD-4.0.0 | 1.85899E-06 | None | None | None | None | N | None | 4.00555E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs569210689 |
0.214 | 0.001 | N | 0.29 | 0.073 | 0.139678290688 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63399E-04 | None | 0 | 0 | 0 |
| A/V | rs569210689 |
0.214 | 0.001 | N | 0.29 | 0.073 | 0.139678290688 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.079E-04 | 0 |
| A/V | rs569210689 |
0.214 | 0.001 | N | 0.29 | 0.073 | 0.139678290688 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/V | rs569210689 |
0.214 | 0.001 | N | 0.29 | 0.073 | 0.139678290688 | gnomAD-4.0.0 | 8.05499E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.42757E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6641 | likely_pathogenic | 0.7061 | pathogenic | -0.729 | Destabilizing | 0.934 | D | 0.649 | neutral | None | None | None | None | N |
| A/D | 0.7259 | likely_pathogenic | 0.7132 | pathogenic | -0.656 | Destabilizing | 0.789 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/E | 0.5614 | ambiguous | 0.5513 | ambiguous | -0.704 | Destabilizing | 0.739 | D | 0.645 | neutral | N | 0.4724735 | None | None | N |
| A/F | 0.5748 | likely_pathogenic | 0.5845 | pathogenic | -0.744 | Destabilizing | 0.649 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/G | 0.1637 | likely_benign | 0.1897 | benign | -0.756 | Destabilizing | 0.446 | N | 0.559 | neutral | N | 0.497254515 | None | None | N |
| A/H | 0.8317 | likely_pathogenic | 0.8397 | pathogenic | -0.813 | Destabilizing | 0.977 | D | 0.716 | prob.delet. | None | None | None | None | N |
| A/I | 0.4051 | ambiguous | 0.3932 | ambiguous | -0.146 | Destabilizing | 0.036 | N | 0.563 | neutral | None | None | None | None | N |
| A/K | 0.7806 | likely_pathogenic | 0.7866 | pathogenic | -0.894 | Destabilizing | 0.789 | D | 0.636 | neutral | None | None | None | None | N |
| A/L | 0.3601 | ambiguous | 0.3593 | ambiguous | -0.146 | Destabilizing | 0.002 | N | 0.357 | neutral | None | None | None | None | N |
| A/M | 0.4006 | ambiguous | 0.4087 | ambiguous | -0.324 | Destabilizing | 0.649 | D | 0.694 | prob.neutral | None | None | None | None | N |
| A/N | 0.655 | likely_pathogenic | 0.6614 | pathogenic | -0.576 | Destabilizing | 0.919 | D | 0.705 | prob.neutral | None | None | None | None | N |
| A/P | 0.6354 | likely_pathogenic | 0.538 | ambiguous | -0.24 | Destabilizing | 0.896 | D | 0.68 | prob.neutral | N | 0.448249847 | None | None | N |
| A/Q | 0.6739 | likely_pathogenic | 0.6918 | pathogenic | -0.713 | Destabilizing | 0.919 | D | 0.7 | prob.neutral | None | None | None | None | N |
| A/R | 0.7319 | likely_pathogenic | 0.7388 | pathogenic | -0.571 | Destabilizing | 0.789 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/S | 0.1705 | likely_benign | 0.1801 | benign | -0.884 | Destabilizing | 0.284 | N | 0.571 | neutral | N | 0.42284997 | None | None | N |
| A/T | 0.1509 | likely_benign | 0.1509 | benign | -0.827 | Destabilizing | 0.284 | N | 0.556 | neutral | N | 0.472646859 | None | None | N |
| A/V | 0.1743 | likely_benign | 0.1712 | benign | -0.24 | Destabilizing | 0.001 | N | 0.29 | neutral | N | 0.44559633 | None | None | N |
| A/W | 0.8792 | likely_pathogenic | 0.8851 | pathogenic | -1.026 | Destabilizing | 0.977 | D | 0.735 | prob.delet. | None | None | None | None | N |
| A/Y | 0.7185 | likely_pathogenic | 0.7243 | pathogenic | -0.622 | Destabilizing | 0.789 | D | 0.705 | prob.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.