Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16251 | 48976;48977;48978 | chr2:178614856;178614855;178614854 | chr2:179479583;179479582;179479581 |
| N2AB | 14610 | 44053;44054;44055 | chr2:178614856;178614855;178614854 | chr2:179479583;179479582;179479581 |
| N2A | 13683 | 41272;41273;41274 | chr2:178614856;178614855;178614854 | chr2:179479583;179479582;179479581 |
| N2B | 7186 | 21781;21782;21783 | chr2:178614856;178614855;178614854 | chr2:179479583;179479582;179479581 |
| Novex-1 | 7311 | 22156;22157;22158 | chr2:178614856;178614855;178614854 | chr2:179479583;179479582;179479581 |
| Novex-2 | 7378 | 22357;22358;22359 | chr2:178614856;178614855;178614854 | chr2:179479583;179479582;179479581 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 1.0 | D | 0.793 | 0.43 | 0.420080204436 | gnomAD-4.0.0 | 7.04304E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.69814E-05 |
| D/N | rs199954570  |
0.512 | 1.0 | D | 0.785 | 0.399 | None | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.08319E-04 | 0 | None | 0 | None | 0 | 5.4E-05 | 1.66058E-04 |
| D/N | rs199954570 |
0.512 | 1.0 | D | 0.785 | 0.399 | None | gnomAD-3.1.2 | 5.93E-05 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.1781E-04 | 0 | 0 |
| D/N | rs199954570 |
0.512 | 1.0 | D | 0.785 | 0.399 | None | gnomAD-4.0.0 | 3.0539E-05 | None | None | None | None | N | None | 0 | 3.7743E-05 | None | 2.07915E-04 | 0 | None | 0 | 1.67056E-04 | 3.19744E-05 | 0 | 3.27923E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4495 | ambiguous | 0.4697 | ambiguous | -0.213 | Destabilizing | 1.0 | D | 0.747 | deleterious | D | 0.526866068 | None | None | N |
| D/C | 0.9213 | likely_pathogenic | 0.9338 | pathogenic | 0.214 | Stabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| D/E | 0.4469 | ambiguous | 0.473 | ambiguous | -0.274 | Destabilizing | 0.999 | D | 0.461 | neutral | N | 0.504366843 | None | None | N |
| D/F | 0.9538 | likely_pathogenic | 0.9552 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| D/G | 0.5132 | ambiguous | 0.5312 | ambiguous | -0.371 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.602248954 | None | None | N |
| D/H | 0.7771 | likely_pathogenic | 0.8037 | pathogenic | -0.197 | Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.62700131 | None | None | N |
| D/I | 0.9207 | likely_pathogenic | 0.9259 | pathogenic | 0.142 | Stabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| D/K | 0.8659 | likely_pathogenic | 0.8845 | pathogenic | 0.435 | Stabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| D/L | 0.8565 | likely_pathogenic | 0.8537 | pathogenic | 0.142 | Stabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| D/M | 0.9502 | likely_pathogenic | 0.9566 | pathogenic | 0.339 | Stabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| D/N | 0.191 | likely_benign | 0.2233 | benign | 0.248 | Stabilizing | 1.0 | D | 0.785 | deleterious | D | 0.57116007 | None | None | N |
| D/P | 0.6775 | likely_pathogenic | 0.6944 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| D/Q | 0.8183 | likely_pathogenic | 0.8387 | pathogenic | 0.249 | Stabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| D/R | 0.9007 | likely_pathogenic | 0.9037 | pathogenic | 0.501 | Stabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| D/S | 0.3053 | likely_benign | 0.3404 | ambiguous | 0.148 | Stabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| D/T | 0.7218 | likely_pathogenic | 0.7498 | pathogenic | 0.266 | Stabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| D/V | 0.7893 | likely_pathogenic | 0.7905 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.795 | deleterious | D | 0.64332485 | None | None | N |
| D/W | 0.9927 | likely_pathogenic | 0.9924 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| D/Y | 0.7936 | likely_pathogenic | 0.7918 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.705385611 | 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.