Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16543 | 49852;49853;49854 | chr2:178613182;178613181;178613180 | chr2:179477909;179477908;179477907 |
| N2AB | 14902 | 44929;44930;44931 | chr2:178613182;178613181;178613180 | chr2:179477909;179477908;179477907 |
| N2A | 13975 | 42148;42149;42150 | chr2:178613182;178613181;178613180 | chr2:179477909;179477908;179477907 |
| N2B | 7478 | 22657;22658;22659 | chr2:178613182;178613181;178613180 | chr2:179477909;179477908;179477907 |
| Novex-1 | 7603 | 23032;23033;23034 | chr2:178613182;178613181;178613180 | chr2:179477909;179477908;179477907 |
| Novex-2 | 7670 | 23233;23234;23235 | chr2:178613182;178613181;178613180 | chr2:179477909;179477908;179477907 |
| 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 | rs753250455  |
-2.654 | 0.682 | D | 0.683 | 0.403 | 0.559082253534 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.09271E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs753250455 |
-2.654 | 0.682 | D | 0.683 | 0.403 | 0.559082253534 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94704E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs753250455 |
-2.654 | 0.682 | D | 0.683 | 0.403 | 0.559082253534 | gnomAD-4.0.0 | 3.10441E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12188E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs756519277 |
-0.993 | 0.003 | N | 0.157 | 0.051 | 0.292787519742 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.69E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs756519277 |
-0.993 | 0.003 | N | 0.157 | 0.051 | 0.292787519742 | gnomAD-4.0.0 | 1.3712E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53627E-05 | None | 0 | 0 | 9.0025E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8831 | likely_pathogenic | 0.8135 | pathogenic | -2.423 | Highly Destabilizing | 0.587 | D | 0.532 | neutral | None | None | None | None | N |
| I/C | 0.9215 | likely_pathogenic | 0.876 | pathogenic | -1.553 | Destabilizing | 0.996 | D | 0.728 | deleterious | None | None | None | None | N |
| I/D | 0.995 | likely_pathogenic | 0.9907 | pathogenic | -2.956 | Highly Destabilizing | 0.984 | D | 0.857 | deleterious | None | None | None | None | N |
| I/E | 0.9796 | likely_pathogenic | 0.9678 | pathogenic | -2.701 | Highly Destabilizing | 0.953 | D | 0.861 | deleterious | None | None | None | None | N |
| I/F | 0.4899 | ambiguous | 0.4047 | ambiguous | -1.518 | Destabilizing | 0.883 | D | 0.719 | prob.delet. | N | 0.473264555 | None | None | N |
| I/G | 0.9853 | likely_pathogenic | 0.9706 | pathogenic | -2.964 | Highly Destabilizing | 0.953 | D | 0.849 | deleterious | None | None | None | None | N |
| I/H | 0.9615 | likely_pathogenic | 0.9331 | pathogenic | -2.41 | Highly Destabilizing | 0.996 | D | 0.801 | deleterious | None | None | None | None | N |
| I/K | 0.9592 | likely_pathogenic | 0.9393 | pathogenic | -1.983 | Destabilizing | 0.953 | D | 0.861 | deleterious | None | None | None | None | N |
| I/L | 0.226 | likely_benign | 0.1882 | benign | -0.842 | Destabilizing | 0.162 | N | 0.423 | neutral | N | 0.463536659 | None | None | N |
| I/M | 0.29 | likely_benign | 0.238 | benign | -0.682 | Destabilizing | 0.883 | D | 0.662 | prob.neutral | D | 0.546522235 | None | None | N |
| I/N | 0.9455 | likely_pathogenic | 0.9026 | pathogenic | -2.462 | Highly Destabilizing | 0.979 | D | 0.839 | deleterious | D | 0.611199551 | None | None | N |
| I/P | 0.9933 | likely_pathogenic | 0.9895 | pathogenic | -1.353 | Destabilizing | 0.984 | D | 0.849 | deleterious | None | None | None | None | N |
| I/Q | 0.9516 | likely_pathogenic | 0.9209 | pathogenic | -2.275 | Highly Destabilizing | 0.984 | D | 0.809 | deleterious | None | None | None | None | N |
| I/R | 0.9391 | likely_pathogenic | 0.9124 | pathogenic | -1.779 | Destabilizing | 0.953 | D | 0.831 | deleterious | None | None | None | None | N |
| I/S | 0.9257 | likely_pathogenic | 0.875 | pathogenic | -3.082 | Highly Destabilizing | 0.883 | D | 0.798 | deleterious | D | 0.609655139 | None | None | N |
| I/T | 0.7879 | likely_pathogenic | 0.6898 | pathogenic | -2.673 | Highly Destabilizing | 0.682 | D | 0.683 | prob.neutral | D | 0.598643597 | None | None | N |
| I/V | 0.084 | likely_benign | 0.0686 | benign | -1.353 | Destabilizing | 0.003 | N | 0.157 | neutral | N | 0.411571153 | None | None | N |
| I/W | 0.9776 | likely_pathogenic | 0.9708 | pathogenic | -1.926 | Destabilizing | 0.996 | D | 0.695 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9013 | likely_pathogenic | 0.8584 | pathogenic | -1.591 | Destabilizing | 0.953 | D | 0.733 | 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.