Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28925 | 86998;86999;87000 | chr2:178559359;178559358;178559357 | chr2:179424086;179424085;179424084 |
| N2AB | 27284 | 82075;82076;82077 | chr2:178559359;178559358;178559357 | chr2:179424086;179424085;179424084 |
| N2A | 26357 | 79294;79295;79296 | chr2:178559359;178559358;178559357 | chr2:179424086;179424085;179424084 |
| N2B | 19860 | 59803;59804;59805 | chr2:178559359;178559358;178559357 | chr2:179424086;179424085;179424084 |
| Novex-1 | 19985 | 60178;60179;60180 | chr2:178559359;178559358;178559357 | chr2:179424086;179424085;179424084 |
| Novex-2 | 20052 | 60379;60380;60381 | chr2:178559359;178559358;178559357 | chr2:179424086;179424085;179424084 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | rs1234811705  |
-0.419 | 0.22 | N | 0.433 | 0.308 | 0.159798565429 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| F/I | rs1234811705 |
-0.419 | 0.22 | N | 0.433 | 0.308 | 0.159798565429 | gnomAD-4.0.0 | 1.36971E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80026E-06 | 0 | 0 |
| F/L | None | None | 0.055 | N | 0.433 | 0.26 | 0.154104182512 | gnomAD-4.0.0 | 6.84855E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00131E-07 | 0 | 0 |
| F/S | rs760480245 |
-0.547 | 0.497 | N | 0.564 | 0.182 | 0.465038187318 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.98E-05 | 0 | None | 0 | None | 0 | 8.9E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8081 | likely_pathogenic | 0.8668 | pathogenic | -1.048 | Destabilizing | 0.272 | N | 0.561 | neutral | None | None | None | None | I |
| F/C | 0.5261 | ambiguous | 0.5825 | pathogenic | -0.32 | Destabilizing | 0.958 | D | 0.631 | neutral | N | 0.434497555 | None | None | I |
| F/D | 0.941 | likely_pathogenic | 0.9526 | pathogenic | 0.722 | Stabilizing | 0.726 | D | 0.639 | neutral | None | None | None | None | I |
| F/E | 0.9577 | likely_pathogenic | 0.9664 | pathogenic | 0.694 | Stabilizing | 0.726 | D | 0.615 | neutral | None | None | None | None | I |
| F/G | 0.9345 | likely_pathogenic | 0.9575 | pathogenic | -1.244 | Destabilizing | 0.726 | D | 0.582 | neutral | None | None | None | None | I |
| F/H | 0.6896 | likely_pathogenic | 0.7085 | pathogenic | 0.15 | Stabilizing | 0.567 | D | 0.51 | neutral | None | None | None | None | I |
| F/I | 0.4579 | ambiguous | 0.4927 | ambiguous | -0.552 | Destabilizing | 0.22 | N | 0.433 | neutral | N | 0.406886879 | None | None | I |
| F/K | 0.9696 | likely_pathogenic | 0.9753 | pathogenic | -0.059 | Destabilizing | 0.567 | D | 0.619 | neutral | None | None | None | None | I |
| F/L | 0.9462 | likely_pathogenic | 0.9554 | pathogenic | -0.552 | Destabilizing | 0.055 | N | 0.433 | neutral | N | 0.42239505 | None | None | I |
| F/M | 0.7335 | likely_pathogenic | 0.765 | pathogenic | -0.361 | Destabilizing | 0.726 | D | 0.417 | neutral | None | None | None | None | I |
| F/N | 0.7476 | likely_pathogenic | 0.777 | pathogenic | 0.03 | Stabilizing | 0.726 | D | 0.639 | neutral | None | None | None | None | I |
| F/P | 0.9978 | likely_pathogenic | 0.9984 | pathogenic | -0.697 | Destabilizing | 0.89 | D | 0.643 | neutral | None | None | None | None | I |
| F/Q | 0.9203 | likely_pathogenic | 0.935 | pathogenic | -0.078 | Destabilizing | 0.726 | D | 0.639 | neutral | None | None | None | None | I |
| F/R | 0.9365 | likely_pathogenic | 0.9475 | pathogenic | 0.465 | Stabilizing | 0.567 | D | 0.638 | neutral | None | None | None | None | I |
| F/S | 0.7274 | likely_pathogenic | 0.7936 | pathogenic | -0.687 | Destabilizing | 0.497 | N | 0.564 | neutral | N | 0.446117271 | None | None | I |
| F/T | 0.8111 | likely_pathogenic | 0.8512 | pathogenic | -0.623 | Destabilizing | 0.567 | D | 0.566 | neutral | None | None | None | None | I |
| F/V | 0.4914 | ambiguous | 0.5419 | ambiguous | -0.697 | Destabilizing | 0.22 | N | 0.475 | neutral | N | 0.378910844 | None | None | I |
| F/W | 0.562 | ambiguous | 0.5658 | pathogenic | -0.368 | Destabilizing | 0.726 | D | 0.44 | neutral | None | None | None | None | I |
| F/Y | 0.1224 | likely_benign | 0.1148 | benign | -0.315 | Destabilizing | None | N | 0.201 | neutral | N | 0.353343183 | None | None | I |
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.