Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28958 | 87097;87098;87099 | chr2:178558587;178558586;178558585 | chr2:179423314;179423313;179423312 |
| N2AB | 27317 | 82174;82175;82176 | chr2:178558587;178558586;178558585 | chr2:179423314;179423313;179423312 |
| N2A | 26390 | 79393;79394;79395 | chr2:178558587;178558586;178558585 | chr2:179423314;179423313;179423312 |
| N2B | 19893 | 59902;59903;59904 | chr2:178558587;178558586;178558585 | chr2:179423314;179423313;179423312 |
| Novex-1 | 20018 | 60277;60278;60279 | chr2:178558587;178558586;178558585 | chr2:179423314;179423313;179423312 |
| Novex-2 | 20085 | 60478;60479;60480 | chr2:178558587;178558586;178558585 | chr2:179423314;179423313;179423312 |
| 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/G | None | None | 1.0 | N | 0.509 | 0.478 | 0.360163838653 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs199639729  |
-1.002 | 0.994 | N | 0.562 | 0.351 | None | gnomAD-2.1.1 | 4.66E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 4E-05 | 8.64E-05 | 0 |
| S/N | rs199639729 |
-1.002 | 0.994 | N | 0.562 | 0.351 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| S/N | rs199639729 |
-1.002 | 0.994 | N | 0.562 | 0.351 | None | gnomAD-4.0.0 | 5.63955E-05 | None | None | None | None | N | None | 1.33451E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62848E-05 | 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 | 0.0949 | likely_benign | 0.0973 | benign | -1.028 | Destabilizing | 0.984 | D | 0.495 | neutral | None | None | None | None | N |
| S/C | 0.1031 | likely_benign | 0.1023 | benign | -0.979 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.48903001 | None | None | N |
| S/D | 0.5288 | ambiguous | 0.5572 | ambiguous | -0.726 | Destabilizing | 1.0 | D | 0.563 | neutral | None | None | None | None | N |
| S/E | 0.5844 | likely_pathogenic | 0.6044 | pathogenic | -0.69 | Destabilizing | 1.0 | D | 0.549 | neutral | None | None | None | None | N |
| S/F | 0.1926 | likely_benign | 0.2058 | benign | -1.321 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| S/G | 0.1245 | likely_benign | 0.1283 | benign | -1.261 | Destabilizing | 1.0 | D | 0.509 | neutral | N | 0.49401676 | None | None | N |
| S/H | 0.3041 | likely_benign | 0.3137 | benign | -1.644 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| S/I | 0.2849 | likely_benign | 0.3115 | benign | -0.498 | Destabilizing | 1.0 | D | 0.836 | deleterious | N | 0.513134973 | None | None | N |
| S/K | 0.6351 | likely_pathogenic | 0.6554 | pathogenic | -0.583 | Destabilizing | 1.0 | D | 0.554 | neutral | None | None | None | None | N |
| S/L | 0.1313 | likely_benign | 0.1437 | benign | -0.498 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| S/M | 0.1883 | likely_benign | 0.1998 | benign | -0.262 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| S/N | 0.1979 | likely_benign | 0.2086 | benign | -0.738 | Destabilizing | 0.994 | D | 0.562 | neutral | N | 0.480267371 | None | None | N |
| S/P | 0.9766 | likely_pathogenic | 0.9751 | pathogenic | -0.645 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| S/Q | 0.4896 | ambiguous | 0.4997 | ambiguous | -0.936 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| S/R | 0.549 | ambiguous | 0.5615 | ambiguous | -0.497 | Destabilizing | 1.0 | D | 0.822 | deleterious | N | 0.49376327 | None | None | N |
| S/T | 0.07 | likely_benign | 0.0727 | benign | -0.756 | Destabilizing | 0.994 | D | 0.511 | neutral | N | 0.468154343 | None | None | N |
| S/V | 0.2481 | likely_benign | 0.2635 | benign | -0.645 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| S/W | 0.4047 | ambiguous | 0.4156 | ambiguous | -1.249 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| S/Y | 0.1927 | likely_benign | 0.2022 | benign | -0.951 | Destabilizing | 1.0 | D | 0.849 | deleterious | 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.