Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13715 | 41368;41369;41370 | chr2:178636584;178636583;178636582 | chr2:179501311;179501310;179501309 |
| N2AB | 12074 | 36445;36446;36447 | chr2:178636584;178636583;178636582 | chr2:179501311;179501310;179501309 |
| N2A | 11147 | 33664;33665;33666 | chr2:178636584;178636583;178636582 | chr2:179501311;179501310;179501309 |
| N2B | 4650 | 14173;14174;14175 | chr2:178636584;178636583;178636582 | chr2:179501311;179501310;179501309 |
| Novex-1 | 4775 | 14548;14549;14550 | chr2:178636584;178636583;178636582 | chr2:179501311;179501310;179501309 |
| Novex-2 | 4842 | 14749;14750;14751 | chr2:178636584;178636583;178636582 | chr2:179501311;179501310;179501309 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs2060468649  |
None | 1.0 | D | 0.823 | 0.385 | 0.45063746488 |
Rees (2021)
| None |
T1P 
|
comp het with R11022* | None | None | N | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Domain unfolded in vitro | None | None | None | None | None | None | None | None | None | None | None |
| A/T | rs1192068092 |
-1.27 | 1.0 | N | 0.769 | 0.296 | 0.18995819373 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| A/T | rs1192068092 |
-1.27 | 1.0 | N | 0.769 | 0.296 | 0.18995819373 | gnomAD-4.0.0 | 6.36801E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14386E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.9296 | likely_pathogenic | 0.9524 | pathogenic | -0.826 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| A/D | 0.9969 | likely_pathogenic | 0.9981 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| A/E | 0.9937 | likely_pathogenic | 0.9957 | pathogenic | -0.801 | Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.536562257 | None | None | N |
| A/F | 0.9906 | likely_pathogenic | 0.994 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/G | 0.7236 | likely_pathogenic | 0.7751 | pathogenic | -1.013 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.43785703 | None | None | N |
| A/H | 0.9963 | likely_pathogenic | 0.9976 | pathogenic | -1.197 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| A/I | 0.9738 | likely_pathogenic | 0.9757 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| A/K | 0.999 | likely_pathogenic | 0.9993 | pathogenic | -0.973 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| A/L | 0.9264 | likely_pathogenic | 0.9404 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| A/M | 0.9713 | likely_pathogenic | 0.9784 | pathogenic | -0.253 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| A/N | 0.9905 | likely_pathogenic | 0.9938 | pathogenic | -0.716 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| A/P | 0.9814 | likely_pathogenic | 0.9844 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.829 | deleterious | N | 0.413194658 | None | None | N |
| A/Q | 0.9882 | likely_pathogenic | 0.9913 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| A/R | 0.9953 | likely_pathogenic | 0.996 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| A/S | 0.4663 | ambiguous | 0.5472 | ambiguous | -1.106 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.440290913 | None | None | N |
| A/T | 0.8547 | likely_pathogenic | 0.8926 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.450628231 | None | None | N |
| A/V | 0.8728 | likely_pathogenic | 0.8929 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.444788607 | None | None | N |
| A/W | 0.999 | likely_pathogenic | 0.9994 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| A/Y | 0.9949 | likely_pathogenic | 0.9967 | pathogenic | -0.788 | Destabilizing | 1.0 | D | 0.845 | 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.