Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21877 | 65854;65855;65856 | chr2:178583174;178583173;178583172 | chr2:179447901;179447900;179447899 |
| N2AB | 20236 | 60931;60932;60933 | chr2:178583174;178583173;178583172 | chr2:179447901;179447900;179447899 |
| N2A | 19309 | 58150;58151;58152 | chr2:178583174;178583173;178583172 | chr2:179447901;179447900;179447899 |
| N2B | 12812 | 38659;38660;38661 | chr2:178583174;178583173;178583172 | chr2:179447901;179447900;179447899 |
| Novex-1 | 12937 | 39034;39035;39036 | chr2:178583174;178583173;178583172 | chr2:179447901;179447900;179447899 |
| Novex-2 | 13004 | 39235;39236;39237 | chr2:178583174;178583173;178583172 | chr2:179447901;179447900;179447899 |
| 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/S | rs72646866  |
-0.574 | 1.0 | N | 0.547 | 0.259 | 0.20549828249 | gnomAD-2.1.1 | 1.01548E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 5.90667E-04 | None | 0 | 5.41E-05 | 1.67168E-04 |
| A/S | rs72646866 |
-0.574 | 1.0 | N | 0.547 | 0.259 | 0.20549828249 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 6.21375E-04 | 0 |
| A/S | rs72646866 |
-0.574 | 1.0 | N | 0.547 | 0.259 | 0.20549828249 |
Taylor (2011)
| None |
ARVC 
|
het | None | None | I | Genetic analysis of TTN in 38 ARVC families, incomplete penetrance | None | None | None | None | None | None | None | None | None | None | None |
| A/S | rs72646866 |
-0.574 | 1.0 | N | 0.547 | 0.259 | 0.20549828249 | gnomAD-4.0.0 | 5.70925E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 9.8912E-04 | 1.78194E-05 | 6.60429E-04 | 8.01847E-05 |
| A/V | None | None | 1.0 | N | 0.627 | 0.353 | 0.250039746154 | gnomAD-4.0.0 | 1.59665E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86849E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.9134 | likely_pathogenic | 0.8941 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| A/D | 0.9687 | likely_pathogenic | 0.9625 | pathogenic | -0.813 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.502386268 | None | None | I |
| A/E | 0.912 | likely_pathogenic | 0.8964 | pathogenic | -0.94 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| A/F | 0.9621 | likely_pathogenic | 0.948 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| A/G | 0.5221 | ambiguous | 0.4839 | ambiguous | -0.77 | Destabilizing | 1.0 | D | 0.531 | neutral | N | 0.497384807 | None | None | I |
| A/H | 0.9652 | likely_pathogenic | 0.9591 | pathogenic | -0.837 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| A/I | 0.9062 | likely_pathogenic | 0.8602 | pathogenic | -0.497 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| A/K | 0.9673 | likely_pathogenic | 0.9563 | pathogenic | -0.979 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| A/L | 0.8865 | likely_pathogenic | 0.8445 | pathogenic | -0.497 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| A/M | 0.8601 | likely_pathogenic | 0.8145 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| A/N | 0.912 | likely_pathogenic | 0.8962 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| A/P | 0.9605 | likely_pathogenic | 0.9419 | pathogenic | -0.509 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.499537964 | None | None | I |
| A/Q | 0.8983 | likely_pathogenic | 0.8778 | pathogenic | -0.904 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| A/R | 0.9385 | likely_pathogenic | 0.919 | pathogenic | -0.485 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| A/S | 0.2568 | likely_benign | 0.2426 | benign | -0.867 | Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.49782581 | None | None | I |
| A/T | 0.6825 | likely_pathogenic | 0.6226 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.453983821 | None | None | I |
| A/V | 0.6521 | likely_pathogenic | 0.5717 | pathogenic | -0.509 | Destabilizing | 1.0 | D | 0.627 | neutral | N | 0.466212037 | None | None | I |
| A/W | 0.9938 | likely_pathogenic | 0.991 | pathogenic | -1.265 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| A/Y | 0.968 | likely_pathogenic | 0.958 | pathogenic | -0.921 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
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.