Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22232 | 66919;66920;66921 | chr2:178581574;178581573;178581572 | chr2:179446301;179446300;179446299 |
| N2AB | 20591 | 61996;61997;61998 | chr2:178581574;178581573;178581572 | chr2:179446301;179446300;179446299 |
| N2A | 19664 | 59215;59216;59217 | chr2:178581574;178581573;178581572 | chr2:179446301;179446300;179446299 |
| N2B | 13167 | 39724;39725;39726 | chr2:178581574;178581573;178581572 | chr2:179446301;179446300;179446299 |
| Novex-1 | 13292 | 40099;40100;40101 | chr2:178581574;178581573;178581572 | chr2:179446301;179446300;179446299 |
| Novex-2 | 13359 | 40300;40301;40302 | chr2:178581574;178581573;178581572 | chr2:179446301;179446300;179446299 |
| 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/A | None | None | 0.939 | D | 0.625 | 0.774 | 0.766354235103 | gnomAD-4.0.0 | 1.59395E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78629E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | rs2047754989  |
-3.064 | 0.997 | D | 0.877 | 0.945 | 0.896239366562 |
Chauveau (2013)
Rees (2021)
| None |
MmD-HD 
|
comp het with N34020Tfs*9 | None | None | N | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Domain unfolded in vitro and cannot be re-folded; Also found in WES prioritisation in 23 families with congenital CM; comp het with N34020fs; recessive inheritance (n = 1, 1 affected (total 2)) | None | None | None | None | None | None | None | None | None | None | None |
| V/L | rs979149024 |
None | 0.76 | N | 0.54 | 0.416 | 0.590315534784 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 | 0.9354 | likely_pathogenic | 0.9485 | pathogenic | -2.75 | Highly Destabilizing | 0.939 | D | 0.625 | neutral | D | 0.550504432 | None | None | N |
| V/C | 0.9679 | likely_pathogenic | 0.9709 | pathogenic | -2.15 | Highly Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | N |
| V/D | 0.998 | likely_pathogenic | 0.9987 | pathogenic | -3.392 | Highly Destabilizing | 0.998 | D | 0.888 | deleterious | None | None | None | None | N |
| V/E | 0.9947 | likely_pathogenic | 0.9961 | pathogenic | -3.106 | Highly Destabilizing | 0.997 | D | 0.877 | deleterious | D | 0.637377264 | None | None | N |
| V/F | 0.9467 | likely_pathogenic | 0.948 | pathogenic | -1.475 | Destabilizing | 0.986 | D | 0.807 | deleterious | None | None | None | None | N |
| V/G | 0.959 | likely_pathogenic | 0.9678 | pathogenic | -3.267 | Highly Destabilizing | 0.997 | D | 0.883 | deleterious | D | 0.637377264 | None | None | N |
| V/H | 0.9987 | likely_pathogenic | 0.999 | pathogenic | -2.938 | Highly Destabilizing | 0.999 | D | 0.876 | deleterious | None | None | None | None | N |
| V/I | 0.0933 | likely_benign | 0.093 | benign | -1.219 | Destabilizing | 0.06 | N | 0.281 | neutral | None | None | None | None | N |
| V/K | 0.9962 | likely_pathogenic | 0.9973 | pathogenic | -2.224 | Highly Destabilizing | 0.993 | D | 0.879 | deleterious | None | None | None | None | N |
| V/L | 0.807 | likely_pathogenic | 0.8118 | pathogenic | -1.219 | Destabilizing | 0.76 | D | 0.54 | neutral | N | 0.504479645 | None | None | N |
| V/M | 0.89 | likely_pathogenic | 0.8981 | pathogenic | -1.549 | Destabilizing | 0.982 | D | 0.693 | prob.neutral | D | 0.53002032 | None | None | N |
| V/N | 0.9923 | likely_pathogenic | 0.9941 | pathogenic | -2.82 | Highly Destabilizing | 0.998 | D | 0.893 | deleterious | None | None | None | None | N |
| V/P | 0.9949 | likely_pathogenic | 0.9968 | pathogenic | -1.718 | Destabilizing | 0.998 | D | 0.881 | deleterious | None | None | None | None | N |
| V/Q | 0.9949 | likely_pathogenic | 0.9962 | pathogenic | -2.497 | Highly Destabilizing | 0.998 | D | 0.885 | deleterious | None | None | None | None | N |
| V/R | 0.9919 | likely_pathogenic | 0.9941 | pathogenic | -2.19 | Highly Destabilizing | 0.998 | D | 0.895 | deleterious | None | None | None | None | N |
| V/S | 0.9787 | likely_pathogenic | 0.9836 | pathogenic | -3.277 | Highly Destabilizing | 0.993 | D | 0.874 | deleterious | None | None | None | None | N |
| V/T | 0.9447 | likely_pathogenic | 0.9563 | pathogenic | -2.865 | Highly Destabilizing | 0.953 | D | 0.684 | prob.neutral | None | None | None | None | N |
| V/W | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -1.928 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| V/Y | 0.9938 | likely_pathogenic | 0.9953 | pathogenic | -1.803 | Destabilizing | 0.998 | D | 0.805 | deleterious | 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.