Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20650 | 62173;62174;62175 | chr2:178589777;178589776;178589775 | chr2:179454504;179454503;179454502 |
| N2AB | 19009 | 57250;57251;57252 | chr2:178589777;178589776;178589775 | chr2:179454504;179454503;179454502 |
| N2A | 18082 | 54469;54470;54471 | chr2:178589777;178589776;178589775 | chr2:179454504;179454503;179454502 |
| N2B | 11585 | 34978;34979;34980 | chr2:178589777;178589776;178589775 | chr2:179454504;179454503;179454502 |
| Novex-1 | 11710 | 35353;35354;35355 | chr2:178589777;178589776;178589775 | chr2:179454504;179454503;179454502 |
| Novex-2 | 11777 | 35554;35555;35556 | chr2:178589777;178589776;178589775 | chr2:179454504;179454503;179454502 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs373298871  |
-0.587 | 0.27 | N | 0.471 | 0.15 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| V/I | rs373298871 |
-0.587 | 0.27 | N | 0.471 | 0.15 | 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 |
| V/I | rs373298871 |
-0.587 | 0.27 | N | 0.471 | 0.15 | None | gnomAD-4.0.0 | 5.57814E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.7818E-06 | 0 | 1.60133E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2454 | likely_benign | 0.2356 | benign | -1.33 | Destabilizing | 0.425 | N | 0.371 | neutral | N | 0.44284768 | None | None | I |
| V/C | 0.7434 | likely_pathogenic | 0.7342 | pathogenic | -0.836 | Destabilizing | 0.995 | D | 0.596 | neutral | None | None | None | None | I |
| V/D | 0.7258 | likely_pathogenic | 0.7015 | pathogenic | -1.4 | Destabilizing | 0.784 | D | 0.658 | neutral | N | 0.494468579 | None | None | I |
| V/E | 0.5535 | ambiguous | 0.5484 | ambiguous | -1.469 | Destabilizing | 0.704 | D | 0.605 | neutral | None | None | None | None | I |
| V/F | 0.2994 | likely_benign | 0.28 | benign | -1.251 | Destabilizing | 0.863 | D | 0.629 | neutral | N | 0.49831696 | None | None | I |
| V/G | 0.4211 | ambiguous | 0.4018 | ambiguous | -1.571 | Destabilizing | 0.642 | D | 0.627 | neutral | N | 0.49727681 | None | None | I |
| V/H | 0.7806 | likely_pathogenic | 0.7829 | pathogenic | -1.045 | Destabilizing | 0.995 | D | 0.676 | prob.neutral | None | None | None | None | I |
| V/I | 0.0889 | likely_benign | 0.0927 | benign | -0.793 | Destabilizing | 0.27 | N | 0.471 | neutral | N | 0.427128866 | None | None | I |
| V/K | 0.5467 | ambiguous | 0.5585 | ambiguous | -1.053 | Destabilizing | 0.704 | D | 0.605 | neutral | None | None | None | None | I |
| V/L | 0.3248 | likely_benign | 0.3223 | benign | -0.793 | Destabilizing | 0.002 | N | 0.218 | neutral | N | 0.426608791 | None | None | I |
| V/M | 0.2596 | likely_benign | 0.2476 | benign | -0.5 | Destabilizing | 0.893 | D | 0.611 | neutral | None | None | None | None | I |
| V/N | 0.5399 | ambiguous | 0.5355 | ambiguous | -0.752 | Destabilizing | 0.944 | D | 0.675 | neutral | None | None | None | None | I |
| V/P | 0.3893 | ambiguous | 0.3965 | ambiguous | -0.938 | Destabilizing | 0.001 | N | 0.414 | neutral | None | None | None | None | I |
| V/Q | 0.5019 | ambiguous | 0.5105 | ambiguous | -1.058 | Destabilizing | 0.944 | D | 0.67 | neutral | None | None | None | None | I |
| V/R | 0.4355 | ambiguous | 0.4462 | ambiguous | -0.397 | Destabilizing | 0.944 | D | 0.675 | prob.neutral | None | None | None | None | I |
| V/S | 0.3799 | ambiguous | 0.3711 | ambiguous | -1.169 | Destabilizing | 0.704 | D | 0.622 | neutral | None | None | None | None | I |
| V/T | 0.2678 | likely_benign | 0.2727 | benign | -1.145 | Destabilizing | 0.495 | N | 0.445 | neutral | None | None | None | None | I |
| V/W | 0.9004 | likely_pathogenic | 0.8967 | pathogenic | -1.337 | Destabilizing | 0.995 | D | 0.691 | prob.neutral | None | None | None | None | I |
| V/Y | 0.6933 | likely_pathogenic | 0.7012 | pathogenic | -1.081 | Destabilizing | 0.981 | D | 0.62 | 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.