Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26775 | 80548;80549;80550 | chr2:178565809;178565808;178565807 | chr2:179430536;179430535;179430534 |
| N2AB | 25134 | 75625;75626;75627 | chr2:178565809;178565808;178565807 | chr2:179430536;179430535;179430534 |
| N2A | 24207 | 72844;72845;72846 | chr2:178565809;178565808;178565807 | chr2:179430536;179430535;179430534 |
| N2B | 17710 | 53353;53354;53355 | chr2:178565809;178565808;178565807 | chr2:179430536;179430535;179430534 |
| Novex-1 | 17835 | 53728;53729;53730 | chr2:178565809;178565808;178565807 | chr2:179430536;179430535;179430534 |
| Novex-2 | 17902 | 53929;53930;53931 | chr2:178565809;178565808;178565807 | chr2:179430536;179430535;179430534 |
| 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/M | rs370589806  |
-0.247 | 0.979 | N | 0.577 | 0.221 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs370589806 |
-0.247 | 0.979 | N | 0.577 | 0.221 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 2.41E-05 | 1.96825E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/M | rs370589806 |
-0.247 | 0.979 | N | 0.577 | 0.221 | None | gnomAD-4.0.0 | 8.67686E-06 | None | None | None | None | N | None | 5.34259E-05 | 6.67089E-05 | None | 0 | 0 | None | 0 | 1.64582E-04 | 4.2385E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3066 | likely_benign | 0.3185 | benign | -1.521 | Destabilizing | 0.269 | N | 0.535 | neutral | N | 0.497645659 | None | None | N |
| V/C | 0.7176 | likely_pathogenic | 0.7468 | pathogenic | -0.78 | Destabilizing | 0.995 | D | 0.735 | deleterious | None | None | None | None | N |
| V/D | 0.8844 | likely_pathogenic | 0.8715 | pathogenic | -1.695 | Destabilizing | 0.953 | D | 0.825 | deleterious | None | None | None | None | N |
| V/E | 0.7023 | likely_pathogenic | 0.682 | pathogenic | -1.509 | Destabilizing | 0.713 | D | 0.724 | deleterious | N | 0.498406127 | None | None | N |
| V/F | 0.2813 | likely_benign | 0.2872 | benign | -0.898 | Destabilizing | 0.939 | D | 0.744 | deleterious | None | None | None | None | N |
| V/G | 0.5045 | ambiguous | 0.5032 | ambiguous | -1.991 | Destabilizing | 0.912 | D | 0.782 | deleterious | N | 0.498913106 | None | None | N |
| V/H | 0.8445 | likely_pathogenic | 0.8472 | pathogenic | -1.547 | Destabilizing | 0.996 | D | 0.846 | deleterious | None | None | None | None | N |
| V/I | 0.0722 | likely_benign | 0.0738 | benign | -0.237 | Destabilizing | 0.001 | N | 0.207 | neutral | None | None | None | None | N |
| V/K | 0.7167 | likely_pathogenic | 0.7164 | pathogenic | -1.116 | Destabilizing | 0.878 | D | 0.723 | deleterious | None | None | None | None | N |
| V/L | 0.2468 | likely_benign | 0.267 | benign | -0.237 | Destabilizing | 0.047 | N | 0.502 | neutral | N | 0.470387144 | None | None | N |
| V/M | 0.1763 | likely_benign | 0.1915 | benign | -0.167 | Destabilizing | 0.979 | D | 0.577 | neutral | N | 0.487303312 | None | None | N |
| V/N | 0.6921 | likely_pathogenic | 0.7067 | pathogenic | -1.358 | Destabilizing | 0.516 | D | 0.86 | deleterious | None | None | None | None | N |
| V/P | 0.9488 | likely_pathogenic | 0.9445 | pathogenic | -0.636 | Destabilizing | 0.684 | D | 0.809 | deleterious | None | None | None | None | N |
| V/Q | 0.6077 | likely_pathogenic | 0.6116 | pathogenic | -1.245 | Destabilizing | 0.912 | D | 0.804 | deleterious | None | None | None | None | N |
| V/R | 0.6923 | likely_pathogenic | 0.6824 | pathogenic | -0.966 | Destabilizing | 0.939 | D | 0.86 | deleterious | None | None | None | None | N |
| V/S | 0.4476 | ambiguous | 0.4533 | ambiguous | -1.952 | Destabilizing | 0.068 | N | 0.577 | neutral | None | None | None | None | N |
| V/T | 0.2665 | likely_benign | 0.2915 | benign | -1.623 | Destabilizing | 0.322 | N | 0.573 | neutral | None | None | None | None | N |
| V/W | 0.9136 | likely_pathogenic | 0.9169 | pathogenic | -1.323 | Destabilizing | 0.999 | D | 0.77 | deleterious | None | None | None | None | N |
| V/Y | 0.7393 | likely_pathogenic | 0.7601 | pathogenic | -0.877 | Destabilizing | 0.969 | D | 0.712 | prob.delet. | 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.