Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5054 | 15385;15386;15387 | chr2:178734764;178734763;178734762 | chr2:179599491;179599490;179599489 |
| N2AB | 4737 | 14434;14435;14436 | chr2:178734764;178734763;178734762 | chr2:179599491;179599490;179599489 |
| N2A | 3810 | 11653;11654;11655 | chr2:178734764;178734763;178734762 | chr2:179599491;179599490;179599489 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 1.0 | D | 0.899 | 0.758 | 0.856532632862 |
Rees (2021) 
| None |
CFTD 
|
comp het with Y24599Mfs*12 (in trans) | disulfide | None | N | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Protein unfolded | None | None | None | None | None | None | None | None | None | None | None |
| C/R | None | None | 1.0 | D | 0.899 | 0.758 | 0.856532632862 | gnomAD-4.0.0 | 1.20032E-06 | None | None | disulfide | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| C/Y | None | None | 1.0 | D | 0.897 | 0.716 | 0.79540345994 | gnomAD-4.0.0 | 1.20032E-06 | None | None | disulfide | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.9222 | likely_pathogenic | 0.933 | pathogenic | -1.844 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | disulfide | None | N |
| C/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.171 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | disulfide | None | N |
| C/E | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -0.951 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | disulfide | None | N |
| C/F | 0.9334 | likely_pathogenic | 0.92 | pathogenic | -1.15 | Destabilizing | 1.0 | D | 0.886 | deleterious | D | 0.791754098 | disulfide | None | N |
| C/G | 0.9213 | likely_pathogenic | 0.9313 | pathogenic | -2.218 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.794438399 | disulfide | None | N |
| C/H | 0.9991 | likely_pathogenic | 0.999 | pathogenic | -2.336 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | disulfide | None | N |
| C/I | 0.9214 | likely_pathogenic | 0.8927 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | disulfide | None | N |
| C/K | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.028 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | disulfide | None | N |
| C/L | 0.8726 | likely_pathogenic | 0.8486 | pathogenic | -0.832 | Destabilizing | 0.999 | D | 0.78 | deleterious | None | None | disulfide | None | N |
| C/M | 0.9655 | likely_pathogenic | 0.96 | pathogenic | 0.188 | Stabilizing | 1.0 | D | 0.834 | deleterious | None | None | disulfide | None | N |
| C/N | 0.999 | likely_pathogenic | 0.9989 | pathogenic | -1.527 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | disulfide | None | N |
| C/P | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -1.146 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | disulfide | None | N |
| C/Q | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -1.125 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | disulfide | None | N |
| C/R | 0.9971 | likely_pathogenic | 0.9968 | pathogenic | -1.359 | Destabilizing | 1.0 | D | 0.899 | deleterious | D | 0.794438399 | disulfide | None | N |
| C/S | 0.9793 | likely_pathogenic | 0.9817 | pathogenic | -1.933 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.794438399 | disulfide | None | N |
| C/T | 0.9837 | likely_pathogenic | 0.9833 | pathogenic | -1.509 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | disulfide | None | N |
| C/V | 0.8343 | likely_pathogenic | 0.7895 | pathogenic | -1.146 | Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | disulfide | None | N |
| C/W | 0.9951 | likely_pathogenic | 0.9945 | pathogenic | -1.402 | Destabilizing | 1.0 | D | 0.86 | deleterious | D | 0.794438399 | disulfide | None | N |
| C/Y | 0.9928 | likely_pathogenic | 0.9915 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.794438399 | disulfide | 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.