Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 82 | 469;470;471 | chr2:178802189;178802188;178802187 | chr2:179666916;179666915;179666914 |
| N2AB | 82 | 469;470;471 | chr2:178802189;178802188;178802187 | chr2:179666916;179666915;179666914 |
| N2A | 82 | 469;470;471 | chr2:178802189;178802188;178802187 | chr2:179666916;179666915;179666914 |
| N2B | 82 | 469;470;471 | chr2:178802189;178802188;178802187 | chr2:179666916;179666915;179666914 |
| Novex-1 | 82 | 469;470;471 | chr2:178802189;178802188;178802187 | chr2:179666916;179666915;179666914 |
| Novex-2 | 82 | 469;470;471 | chr2:178802189;178802188;178802187 | chr2:179666916;179666915;179666914 |
| Novex-3 | 82 | 469;470;471 | chr2:178802189;178802188;178802187 | chr2:179666916;179666915;179666914 |
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/D | None | None | 1.0 | D | 0.898 | 0.783 | 0.901813502436 |
Rees (2021) 
| None |
CFTD 
|
comp het with R34807Sfs*7 (in trans) | None | -1.93(TCAP) | N | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Protein unfolded; Tm 37 degrees lower than WT | None | None | None | None | None | None | None | None | None | None | None |
| A/T | rs1575010544 |
None | 1.0 | D | 0.789 | 0.784 | 0.653846678015 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -1.555(TCAP) | N | None | 0 | 0 | 0 | 0 | 1.92678E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs1575010544 |
None | 1.0 | D | 0.789 | 0.784 | 0.653846678015 | gnomAD-4.0.0 | 3.09756E-06 | None | None | None | -1.555(TCAP) | N | None | 0 | 0 | None | 0 | 6.68479E-05 | None | 0 | 0 | 0 | 1.09791E-05 | 1.59995E-05 |
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 | 0.9757 | likely_pathogenic | 0.9666 | pathogenic | -1.613 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | -2.149(TCAP) | N |
| A/D | 0.9967 | likely_pathogenic | 0.9965 | pathogenic | -2.797 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | D | 0.858021745 | None | -1.93(TCAP) | N |
| A/E | 0.9928 | likely_pathogenic | 0.9929 | pathogenic | -2.614 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | -2.117(TCAP) | N |
| A/F | 0.9775 | likely_pathogenic | 0.9737 | pathogenic | -0.808 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | -1.084(TCAP) | N |
| A/G | 0.4953 | ambiguous | 0.4409 | ambiguous | -1.779 | Destabilizing | 1.0 | D | 0.547 | neutral | D | 0.755774081 | None | -0.587(TCAP) | N |
| A/H | 0.9981 | likely_pathogenic | 0.9979 | pathogenic | -2.02 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | -0.722(TCAP) | N |
| A/I | 0.9008 | likely_pathogenic | 0.8702 | pathogenic | -0.148 | Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | -1.19(TCAP) | N |
| A/K | 0.9986 | likely_pathogenic | 0.9986 | pathogenic | -1.39 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | -2.245(TCAP) | N |
| A/L | 0.8495 | likely_pathogenic | 0.822 | pathogenic | -0.148 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | -1.19(TCAP) | N |
| A/M | 0.9406 | likely_pathogenic | 0.9278 | pathogenic | -0.571 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | -1.561(TCAP) | N |
| A/N | 0.9948 | likely_pathogenic | 0.9939 | pathogenic | -1.727 | Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | -1.538(TCAP) | N |
| A/P | 0.9952 | likely_pathogenic | 0.9936 | pathogenic | -0.504 | Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.858675096 | None | -1.026(TCAP) | N |
| A/Q | 0.9916 | likely_pathogenic | 0.9916 | pathogenic | -1.573 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | -1.765(TCAP) | N |
| A/R | 0.9937 | likely_pathogenic | 0.9939 | pathogenic | -1.398 | Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | -2.089(TCAP) | N |
| A/S | 0.6274 | likely_pathogenic | 0.587 | pathogenic | -2.098 | Highly Destabilizing | 1.0 | D | 0.549 | neutral | D | 0.791428801 | None | -1.346(TCAP) | N |
| A/T | 0.8169 | likely_pathogenic | 0.7815 | pathogenic | -1.801 | Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.826307074 | None | -1.555(TCAP) | N |
| A/V | 0.6277 | likely_pathogenic | 0.5747 | pathogenic | -0.504 | Destabilizing | 1.0 | D | 0.633 | neutral | D | 0.570506986 | None | -1.026(TCAP) | N |
| A/W | 0.9989 | likely_pathogenic | 0.9987 | pathogenic | -1.525 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | -1.418(TCAP) | N |
| A/Y | 0.9938 | likely_pathogenic | 0.9932 | pathogenic | -1.042 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | -1.069(TCAP) | 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.