Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19517 | 58774;58775;58776 | chr2:178593751;178593750;178593749 | chr2:179458478;179458477;179458476 |
| N2AB | 17876 | 53851;53852;53853 | chr2:178593751;178593750;178593749 | chr2:179458478;179458477;179458476 |
| N2A | 16949 | 51070;51071;51072 | chr2:178593751;178593750;178593749 | chr2:179458478;179458477;179458476 |
| N2B | 10452 | 31579;31580;31581 | chr2:178593751;178593750;178593749 | chr2:179458478;179458477;179458476 |
| Novex-1 | 10577 | 31954;31955;31956 | chr2:178593751;178593750;178593749 | chr2:179458478;179458477;179458476 |
| Novex-2 | 10644 | 32155;32156;32157 | chr2:178593751;178593750;178593749 | chr2:179458478;179458477;179458476 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs72646838  |
-3.215 | 0.201 | D | 0.669 | 0.515 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/T | rs72646838 |
-3.215 | 0.201 | D | 0.669 | 0.515 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 9.49367E-03 | 1.47E-05 | 0 | 4.78927E-04 |
| I/T | rs72646838 |
-3.215 | 0.201 | D | 0.669 | 0.515 | None |
Taylor (2011)
| None |
ARVC 
|
het | None | None | N | Genetic analysis of TTN in 38 ARVC families, incomplete penetrance | None | None | None | None | None | None | None | None | None | None | None |
| I/T | rs72646838 |
-3.215 | 0.201 | D | 0.669 | 0.515 | None | gnomAD-4.0.0 | 1.6116E-05 | None | None | None | None | N | None | 0 | 1.66817E-05 | None | 0 | 0 | None | 0 | 9.90753E-04 | 1.52591E-05 | 0 | 1.60113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8493 | likely_pathogenic | 0.8347 | pathogenic | -2.989 | Highly Destabilizing | 0.25 | N | 0.671 | neutral | None | None | None | None | N |
| I/C | 0.9427 | likely_pathogenic | 0.9351 | pathogenic | -2.432 | Highly Destabilizing | 0.947 | D | 0.768 | deleterious | None | None | None | None | N |
| I/D | 0.9984 | likely_pathogenic | 0.9983 | pathogenic | -3.622 | Highly Destabilizing | 0.826 | D | 0.897 | deleterious | None | None | None | None | N |
| I/E | 0.9931 | likely_pathogenic | 0.9931 | pathogenic | -3.363 | Highly Destabilizing | 0.826 | D | 0.894 | deleterious | None | None | None | None | N |
| I/F | 0.7491 | likely_pathogenic | 0.716 | pathogenic | -1.775 | Destabilizing | 0.638 | D | 0.653 | neutral | D | 0.527075399 | None | None | N |
| I/G | 0.9898 | likely_pathogenic | 0.9891 | pathogenic | -3.564 | Highly Destabilizing | 0.826 | D | 0.889 | deleterious | None | None | None | None | N |
| I/H | 0.994 | likely_pathogenic | 0.9931 | pathogenic | -3.02 | Highly Destabilizing | 0.982 | D | 0.886 | deleterious | None | None | None | None | N |
| I/K | 0.9894 | likely_pathogenic | 0.9882 | pathogenic | -2.461 | Highly Destabilizing | 0.826 | D | 0.895 | deleterious | None | None | None | None | N |
| I/L | 0.2737 | likely_benign | 0.279 | benign | -1.292 | Destabilizing | 0.043 | N | 0.33 | neutral | N | 0.496300949 | None | None | N |
| I/M | 0.3565 | ambiguous | 0.3381 | benign | -1.379 | Destabilizing | 0.638 | D | 0.647 | neutral | N | 0.4906134 | None | None | N |
| I/N | 0.9829 | likely_pathogenic | 0.9823 | pathogenic | -2.937 | Highly Destabilizing | 0.916 | D | 0.91 | deleterious | D | 0.527328889 | None | None | N |
| I/P | 0.9945 | likely_pathogenic | 0.9942 | pathogenic | -1.843 | Destabilizing | 0.935 | D | 0.9 | deleterious | None | None | None | None | N |
| I/Q | 0.9889 | likely_pathogenic | 0.9883 | pathogenic | -2.746 | Highly Destabilizing | 0.935 | D | 0.912 | deleterious | None | None | None | None | N |
| I/R | 0.9829 | likely_pathogenic | 0.9804 | pathogenic | -2.149 | Highly Destabilizing | 0.826 | D | 0.912 | deleterious | None | None | None | None | N |
| I/S | 0.951 | likely_pathogenic | 0.9493 | pathogenic | -3.602 | Highly Destabilizing | 0.638 | D | 0.826 | deleterious | D | 0.527328889 | None | None | N |
| I/T | 0.715 | likely_pathogenic | 0.6856 | pathogenic | -3.196 | Highly Destabilizing | 0.201 | N | 0.669 | neutral | D | 0.527075399 | None | None | N |
| I/V | 0.0914 | likely_benign | 0.0852 | benign | -1.843 | Destabilizing | 0.001 | N | 0.195 | neutral | N | 0.400187407 | None | None | N |
| I/W | 0.9918 | likely_pathogenic | 0.9892 | pathogenic | -2.227 | Highly Destabilizing | 0.982 | D | 0.855 | deleterious | None | None | None | None | N |
| I/Y | 0.9771 | likely_pathogenic | 0.974 | pathogenic | -2.0 | Highly Destabilizing | 0.826 | D | 0.755 | 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.