Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26006 | 78241;78242;78243 | chr2:178568116;178568115;178568114 | chr2:179432843;179432842;179432841 |
| N2AB | 24365 | 73318;73319;73320 | chr2:178568116;178568115;178568114 | chr2:179432843;179432842;179432841 |
| N2A | 23438 | 70537;70538;70539 | chr2:178568116;178568115;178568114 | chr2:179432843;179432842;179432841 |
| N2B | 16941 | 51046;51047;51048 | chr2:178568116;178568115;178568114 | chr2:179432843;179432842;179432841 |
| Novex-1 | 17066 | 51421;51422;51423 | chr2:178568116;178568115;178568114 | chr2:179432843;179432842;179432841 |
| Novex-2 | 17133 | 51622;51623;51624 | chr2:178568116;178568115;178568114 | chr2:179432843;179432842;179432841 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | rs749079480  |
None | None | N | 0.193 | 0.073 | 0.104622674875 | gnomAD-4.0.0 | 1.59204E-06 | None | None | None | None | N | None | 0 | 2.28749E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs749079480 |
-0.908 | 0.001 | N | 0.199 | 0.048 | 0.0846915920261 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| S/T | rs749079480 |
-0.908 | 0.001 | N | 0.199 | 0.048 | 0.0846915920261 | gnomAD-4.0.0 | 1.59204E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8595E-06 | 0 | 0 |
| S/Y | None | None | None | N | 0.423 | 0.222 | 0.42130639912 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.94099E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.083 | likely_benign | 0.0914 | benign | -0.446 | Destabilizing | None | N | 0.193 | neutral | N | 0.518911237 | None | None | N |
| S/C | 0.0692 | likely_benign | 0.0712 | benign | -0.668 | Destabilizing | 0.612 | D | 0.647 | neutral | N | 0.479977883 | None | None | N |
| S/D | 0.5193 | ambiguous | 0.5456 | ambiguous | -1.672 | Destabilizing | 0.072 | N | 0.567 | neutral | None | None | None | None | N |
| S/E | 0.5736 | likely_pathogenic | 0.6138 | pathogenic | -1.632 | Destabilizing | 0.072 | N | 0.516 | neutral | None | None | None | None | N |
| S/F | 0.1083 | likely_benign | 0.1243 | benign | -0.721 | Destabilizing | None | N | 0.5 | neutral | D | 0.524165128 | None | None | N |
| S/G | 0.1005 | likely_benign | 0.0949 | benign | -0.702 | Destabilizing | 0.016 | N | 0.433 | neutral | None | None | None | None | N |
| S/H | 0.231 | likely_benign | 0.2524 | benign | -1.282 | Destabilizing | 0.214 | N | 0.665 | neutral | None | None | None | None | N |
| S/I | 0.2013 | likely_benign | 0.2285 | benign | 0.134 | Stabilizing | 0.038 | N | 0.615 | neutral | None | None | None | None | N |
| S/K | 0.693 | likely_pathogenic | 0.734 | pathogenic | -0.748 | Destabilizing | 0.072 | N | 0.517 | neutral | None | None | None | None | N |
| S/L | 0.1122 | likely_benign | 0.1243 | benign | 0.134 | Stabilizing | 0.016 | N | 0.47 | neutral | None | None | None | None | N |
| S/M | 0.1549 | likely_benign | 0.1688 | benign | 0.414 | Stabilizing | 0.356 | N | 0.662 | neutral | None | None | None | None | N |
| S/N | 0.1378 | likely_benign | 0.1376 | benign | -1.123 | Destabilizing | 0.136 | N | 0.579 | neutral | None | None | None | None | N |
| S/P | 0.9647 | likely_pathogenic | 0.9712 | pathogenic | -0.026 | Destabilizing | 0.171 | N | 0.679 | prob.neutral | N | 0.513957894 | None | None | N |
| S/Q | 0.4497 | ambiguous | 0.48 | ambiguous | -1.289 | Destabilizing | 0.356 | N | 0.621 | neutral | None | None | None | None | N |
| S/R | 0.5969 | likely_pathogenic | 0.6386 | pathogenic | -0.635 | Destabilizing | 0.214 | N | 0.68 | prob.neutral | None | None | None | None | N |
| S/T | 0.0822 | likely_benign | 0.0859 | benign | -0.854 | Destabilizing | 0.001 | N | 0.199 | neutral | N | 0.476235108 | None | None | N |
| S/V | 0.1885 | likely_benign | 0.2181 | benign | -0.026 | Destabilizing | 0.038 | N | 0.516 | neutral | None | None | None | None | N |
| S/W | 0.2764 | likely_benign | 0.3123 | benign | -0.882 | Destabilizing | 0.676 | D | 0.688 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1199 | likely_benign | 0.1393 | benign | -0.49 | Destabilizing | None | N | 0.423 | neutral | N | 0.484964632 | 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.