Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19326 | 58201;58202;58203 | chr2:178594518;178594517;178594516 | chr2:179459245;179459244;179459243 |
| N2AB | 17685 | 53278;53279;53280 | chr2:178594518;178594517;178594516 | chr2:179459245;179459244;179459243 |
| N2A | 16758 | 50497;50498;50499 | chr2:178594518;178594517;178594516 | chr2:179459245;179459244;179459243 |
| N2B | 10261 | 31006;31007;31008 | chr2:178594518;178594517;178594516 | chr2:179459245;179459244;179459243 |
| Novex-1 | 10386 | 31381;31382;31383 | chr2:178594518;178594517;178594516 | chr2:179459245;179459244;179459243 |
| Novex-2 | 10453 | 31582;31583;31584 | chr2:178594518;178594517;178594516 | chr2:179459245;179459244;179459243 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.998 | N | 0.703 | 0.268 | 0.499985177359 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/M | rs763120020  |
-0.576 | 0.998 | N | 0.686 | 0.18 | 0.45470266194 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/M | rs763120020 |
-0.576 | 0.998 | N | 0.686 | 0.18 | 0.45470266194 | gnomAD-4.0.0 | 3.42184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49818E-06 | 0 | 0 |
| I/T | rs766571281 |
-1.675 | 0.989 | N | 0.596 | 0.441 | 0.564429724435 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 4.64E-05 | 1.78E-05 | 0 |
| I/T | rs766571281 |
-1.675 | 0.989 | N | 0.596 | 0.441 | 0.564429724435 | gnomAD-4.0.0 | 6.15935E-06 | None | None | None | None | N | None | 2.98954E-05 | 0 | None | 0 | 5.04592E-05 | None | 1.87266E-05 | 0 | 3.59856E-06 | 0 | 1.65684E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3647 | ambiguous | 0.2501 | benign | -1.403 | Destabilizing | 0.992 | D | 0.561 | neutral | None | None | None | None | N |
| I/C | 0.857 | likely_pathogenic | 0.7888 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| I/D | 0.9468 | likely_pathogenic | 0.8736 | pathogenic | -0.592 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/E | 0.8599 | likely_pathogenic | 0.7144 | pathogenic | -0.6 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| I/F | 0.3762 | ambiguous | 0.2724 | benign | -0.925 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | N | 0.500818548 | None | None | N |
| I/G | 0.8705 | likely_pathogenic | 0.7727 | pathogenic | -1.705 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/H | 0.8511 | likely_pathogenic | 0.6877 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/K | 0.7356 | likely_pathogenic | 0.4958 | ambiguous | -0.874 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| I/L | 0.1732 | likely_benign | 0.1391 | benign | -0.662 | Destabilizing | 0.889 | D | 0.254 | neutral | N | 0.457238342 | None | None | N |
| I/M | 0.1496 | likely_benign | 0.1221 | benign | -0.541 | Destabilizing | 0.998 | D | 0.686 | prob.neutral | N | 0.518884234 | None | None | N |
| I/N | 0.735 | likely_pathogenic | 0.5449 | ambiguous | -0.68 | Destabilizing | 0.999 | D | 0.744 | deleterious | N | 0.477037611 | None | None | N |
| I/P | 0.6968 | likely_pathogenic | 0.5884 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/Q | 0.7314 | likely_pathogenic | 0.5592 | ambiguous | -0.85 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/R | 0.6297 | likely_pathogenic | 0.4003 | ambiguous | -0.293 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| I/S | 0.5526 | ambiguous | 0.3907 | ambiguous | -1.307 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | N | 0.456256907 | None | None | N |
| I/T | 0.2225 | likely_benign | 0.1466 | benign | -1.198 | Destabilizing | 0.989 | D | 0.596 | neutral | N | 0.458873138 | None | None | N |
| I/V | 0.1135 | likely_benign | 0.0929 | benign | -0.876 | Destabilizing | 0.333 | N | 0.173 | neutral | N | 0.393610938 | None | None | N |
| I/W | 0.8718 | likely_pathogenic | 0.8284 | pathogenic | -0.964 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/Y | 0.8212 | likely_pathogenic | 0.7273 | pathogenic | -0.746 | Destabilizing | 1.0 | D | 0.679 | 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.