Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7739 | 23440;23441;23442 | chr2:178720547;178720546;178720545 | chr2:179585274;179585273;179585272 |
| N2AB | 7422 | 22489;22490;22491 | chr2:178720547;178720546;178720545 | chr2:179585274;179585273;179585272 |
| N2A | 6495 | 19708;19709;19710 | chr2:178720547;178720546;178720545 | chr2:179585274;179585273;179585272 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs372250586  |
0.062 | 0.006 | N | 0.241 | 0.17 | 0.154104182512 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/G | rs372250586 |
0.062 | 0.006 | N | 0.241 | 0.17 | 0.154104182512 | gnomAD-4.0.0 | 1.23188E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43941E-05 | 0 | 3.31488E-05 |
| R/Q | rs749882000 |
0.044 | 0.966 | N | 0.427 | 0.123 | 0.115124310173 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 1.24131E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| R/Q | rs749882000 |
0.044 | 0.966 | N | 0.427 | 0.123 | 0.115124310173 | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02944E-04 | 0 | 0 |
| R/Q | rs749882000 |
0.044 | 0.966 | N | 0.427 | 0.123 | 0.115124310173 | gnomAD-4.0.0 | 1.17764E-05 | None | None | None | None | N | None | 7.99979E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32537E-06 | 2.19674E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7688 | likely_pathogenic | 0.7708 | pathogenic | 0.043 | Stabilizing | 0.037 | N | 0.235 | neutral | None | None | None | None | N |
| R/C | 0.5008 | ambiguous | 0.4957 | ambiguous | -0.253 | Destabilizing | 0.998 | D | 0.372 | neutral | None | None | None | None | N |
| R/D | 0.8707 | likely_pathogenic | 0.8689 | pathogenic | -0.369 | Destabilizing | 0.872 | D | 0.461 | neutral | None | None | None | None | N |
| R/E | 0.7076 | likely_pathogenic | 0.7151 | pathogenic | -0.333 | Destabilizing | 0.737 | D | 0.363 | neutral | None | None | None | None | N |
| R/F | 0.866 | likely_pathogenic | 0.8702 | pathogenic | -0.289 | Destabilizing | 0.993 | D | 0.4 | neutral | None | None | None | None | N |
| R/G | 0.327 | likely_benign | 0.3103 | benign | -0.086 | Destabilizing | 0.006 | N | 0.241 | neutral | N | 0.311743624 | None | None | N |
| R/H | 0.1934 | likely_benign | 0.2008 | benign | -0.595 | Destabilizing | 0.993 | D | 0.382 | neutral | None | None | None | None | N |
| R/I | 0.7462 | likely_pathogenic | 0.7626 | pathogenic | 0.334 | Stabilizing | 0.98 | D | 0.445 | neutral | None | None | None | None | N |
| R/K | 0.1255 | likely_benign | 0.1282 | benign | -0.192 | Destabilizing | 0.037 | N | 0.2 | neutral | None | None | None | None | N |
| R/L | 0.6578 | likely_pathogenic | 0.672 | pathogenic | 0.334 | Stabilizing | 0.929 | D | 0.41 | neutral | N | 0.480450771 | None | None | N |
| R/M | 0.6333 | likely_pathogenic | 0.6418 | pathogenic | -0.102 | Destabilizing | 0.993 | D | 0.405 | neutral | None | None | None | None | N |
| R/N | 0.784 | likely_pathogenic | 0.7804 | pathogenic | -0.112 | Destabilizing | 0.872 | D | 0.386 | neutral | None | None | None | None | N |
| R/P | 0.915 | likely_pathogenic | 0.9303 | pathogenic | 0.254 | Stabilizing | 0.963 | D | 0.46 | neutral | N | 0.506501221 | None | None | N |
| R/Q | 0.1745 | likely_benign | 0.1808 | benign | -0.138 | Destabilizing | 0.966 | D | 0.427 | neutral | N | 0.44599148 | None | None | N |
| R/S | 0.7749 | likely_pathogenic | 0.7713 | pathogenic | -0.25 | Destabilizing | 0.209 | N | 0.261 | neutral | None | None | None | None | N |
| R/T | 0.6629 | likely_pathogenic | 0.6574 | pathogenic | -0.115 | Destabilizing | 0.584 | D | 0.419 | neutral | None | None | None | None | N |
| R/V | 0.8141 | likely_pathogenic | 0.8265 | pathogenic | 0.254 | Stabilizing | 0.872 | D | 0.471 | neutral | None | None | None | None | N |
| R/W | 0.3639 | ambiguous | 0.3744 | ambiguous | -0.496 | Destabilizing | 0.998 | D | 0.37 | neutral | None | None | None | None | N |
| R/Y | 0.7237 | likely_pathogenic | 0.7289 | pathogenic | -0.096 | Destabilizing | 0.993 | D | 0.403 | neutral | 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.