Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31426 | 94501;94502;94503 | chr2:178547249;178547248;178547247 | chr2:179411976;179411975;179411974 |
| N2AB | 29785 | 89578;89579;89580 | chr2:178547249;178547248;178547247 | chr2:179411976;179411975;179411974 |
| N2A | 28858 | 86797;86798;86799 | chr2:178547249;178547248;178547247 | chr2:179411976;179411975;179411974 |
| N2B | 22361 | 67306;67307;67308 | chr2:178547249;178547248;178547247 | chr2:179411976;179411975;179411974 |
| Novex-1 | 22486 | 67681;67682;67683 | chr2:178547249;178547248;178547247 | chr2:179411976;179411975;179411974 |
| Novex-2 | 22553 | 67882;67883;67884 | chr2:178547249;178547248;178547247 | chr2:179411976;179411975;179411974 |
| 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/F | rs369284856  |
-0.292 | 0.003 | N | 0.509 | 0.304 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 1.29216E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs369284856 |
-0.292 | 0.003 | N | 0.509 | 0.304 | 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 |
| S/F | rs369284856 |
-0.292 | 0.003 | N | 0.509 | 0.304 | None | gnomAD-4.0.0 | 2.56221E-06 | None | None | None | None | N | None | 3.38226E-05 | 0 | None | 0 | 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 | 0.0646 | likely_benign | 0.0751 | benign | -0.692 | Destabilizing | 0.001 | N | 0.239 | neutral | N | 0.430497245 | None | None | N |
| S/C | 0.1061 | likely_benign | 0.1123 | benign | -0.618 | Destabilizing | 0.928 | D | 0.626 | neutral | N | 0.473018658 | None | None | N |
| S/D | 0.6249 | likely_pathogenic | 0.6448 | pathogenic | -1.726 | Destabilizing | 0.563 | D | 0.614 | neutral | None | None | None | None | N |
| S/E | 0.6535 | likely_pathogenic | 0.6768 | pathogenic | -1.516 | Destabilizing | 0.388 | N | 0.613 | neutral | None | None | None | None | N |
| S/F | 0.2039 | likely_benign | 0.2615 | benign | -0.316 | Destabilizing | 0.003 | N | 0.509 | neutral | N | 0.443042468 | None | None | N |
| S/G | 0.1125 | likely_benign | 0.1069 | benign | -1.096 | Destabilizing | 0.001 | N | 0.259 | neutral | None | None | None | None | N |
| S/H | 0.4329 | ambiguous | 0.4381 | ambiguous | -1.523 | Destabilizing | 0.981 | D | 0.633 | neutral | None | None | None | None | N |
| S/I | 0.1963 | likely_benign | 0.2218 | benign | 0.343 | Stabilizing | 0.527 | D | 0.683 | prob.neutral | None | None | None | None | N |
| S/K | 0.8633 | likely_pathogenic | 0.8732 | pathogenic | -0.65 | Destabilizing | 0.388 | N | 0.615 | neutral | None | None | None | None | N |
| S/L | 0.1092 | likely_benign | 0.1312 | benign | 0.343 | Stabilizing | 0.241 | N | 0.623 | neutral | None | None | None | None | N |
| S/M | 0.1708 | likely_benign | 0.1936 | benign | 0.14 | Stabilizing | 0.944 | D | 0.632 | neutral | None | None | None | None | N |
| S/N | 0.2011 | likely_benign | 0.1914 | benign | -1.39 | Destabilizing | 0.388 | N | 0.604 | neutral | None | None | None | None | N |
| S/P | 0.9516 | likely_pathogenic | 0.9712 | pathogenic | 0.032 | Stabilizing | 0.773 | D | 0.689 | prob.neutral | N | 0.49143106 | None | None | N |
| S/Q | 0.6117 | likely_pathogenic | 0.6204 | pathogenic | -1.002 | Destabilizing | 0.818 | D | 0.662 | neutral | None | None | None | None | N |
| S/R | 0.8135 | likely_pathogenic | 0.8207 | pathogenic | -1.107 | Destabilizing | 0.69 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/T | 0.0868 | likely_benign | 0.0917 | benign | -0.957 | Destabilizing | 0.324 | N | 0.577 | neutral | N | 0.338816448 | None | None | N |
| S/V | 0.1686 | likely_benign | 0.2022 | benign | 0.032 | Stabilizing | 0.241 | N | 0.639 | neutral | None | None | None | None | N |
| S/W | 0.3927 | ambiguous | 0.4549 | ambiguous | -0.771 | Destabilizing | 0.981 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1844 | likely_benign | 0.2304 | benign | -0.296 | Destabilizing | 0.457 | N | 0.687 | prob.neutral | N | 0.45651041 | 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.