Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4659 | 14200;14201;14202 | chr2:178739258;178739257;178739256 | chr2:179603985;179603984;179603983 |
| N2AB | 4342 | 13249;13250;13251 | chr2:178739258;178739257;178739256 | chr2:179603985;179603984;179603983 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4296 | 13111;13112;13113 | chr2:178739258;178739257;178739256 | chr2:179603985;179603984;179603983 |
| Novex-1 | 4421 | 13486;13487;13488 | chr2:178739258;178739257;178739256 | chr2:179603985;179603984;179603983 |
| Novex-2 | 4488 | 13687;13688;13689 | chr2:178739258;178739257;178739256 | chr2:179603985;179603984;179603983 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs34706803  |
-2.351 | 1.0 | N | 0.768 | 0.506 | None | gnomAD-2.1.1 | 1.3346E-03 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 3.17663E-02 | 0 | None | 0 | None | 0 | 2.8297E-04 | 1.56206E-03 |
| Y/C | rs34706803 |
-2.351 | 1.0 | N | 0.768 | 0.506 | None | gnomAD-3.1.2 | 7.88302E-04 | None | None | None | None | N | None | 2.41E-05 | 1.3089E-04 | 0 | 2.76498E-02 | 0 | None | 0 | 0 | 2.64558E-04 | 0 | 1.43267E-03 |
| Y/C | rs34706803 |
-2.351 | 1.0 | N | 0.768 | 0.506 | None | gnomAD-4.0.0 | 8.09016E-04 | None | None | None | None | N | None | 2.67322E-05 | 5.01672E-05 | None | 3.34783E-02 | 0 | None | 0 | 0 | 1.42885E-04 | 0 | 2.2983E-03 |
| Y/H | rs779449934 |
-1.841 | 0.997 | N | 0.747 | 0.31 | None | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 2.92E-05 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 0 | 0 |
| Y/H | rs779449934 |
-1.841 | 0.997 | N | 0.747 | 0.31 | None | gnomAD-4.0.0 | 3.43391E-06 | None | None | None | None | N | None | 0 | 2.24628E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 4.65929E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6761 | likely_pathogenic | 0.6479 | pathogenic | -2.945 | Highly Destabilizing | 0.983 | D | 0.719 | prob.delet. | None | None | None | None | N |
| Y/C | 0.1913 | likely_benign | 0.246 | benign | -2.058 | Highly Destabilizing | 1.0 | D | 0.768 | deleterious | N | 0.45002531 | None | None | N |
| Y/D | 0.7632 | likely_pathogenic | 0.7494 | pathogenic | -2.666 | Highly Destabilizing | 0.987 | D | 0.789 | deleterious | D | 0.550493772 | None | None | N |
| Y/E | 0.8847 | likely_pathogenic | 0.8825 | pathogenic | -2.535 | Highly Destabilizing | 0.995 | D | 0.741 | deleterious | None | None | None | None | N |
| Y/F | 0.1125 | likely_benign | 0.1128 | benign | -1.275 | Destabilizing | 0.996 | D | 0.626 | neutral | N | 0.472877887 | None | None | N |
| Y/G | 0.7296 | likely_pathogenic | 0.7122 | pathogenic | -3.308 | Highly Destabilizing | 0.983 | D | 0.765 | deleterious | None | None | None | None | N |
| Y/H | 0.199 | likely_benign | 0.1732 | benign | -1.7 | Destabilizing | 0.997 | D | 0.747 | deleterious | N | 0.439789559 | None | None | N |
| Y/I | 0.648 | likely_pathogenic | 0.6468 | pathogenic | -1.785 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | N |
| Y/K | 0.8087 | likely_pathogenic | 0.8039 | pathogenic | -1.799 | Destabilizing | 0.995 | D | 0.739 | prob.delet. | None | None | None | None | N |
| Y/L | 0.6315 | likely_pathogenic | 0.6243 | pathogenic | -1.785 | Destabilizing | 0.992 | D | 0.699 | prob.neutral | None | None | None | None | N |
| Y/M | 0.7616 | likely_pathogenic | 0.7489 | pathogenic | -1.699 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/N | 0.4187 | ambiguous | 0.4014 | ambiguous | -2.294 | Highly Destabilizing | 0.241 | N | 0.629 | neutral | D | 0.549615923 | None | None | N |
| Y/P | 0.9817 | likely_pathogenic | 0.9835 | pathogenic | -2.177 | Highly Destabilizing | 0.999 | D | 0.836 | deleterious | None | None | None | None | N |
| Y/Q | 0.7082 | likely_pathogenic | 0.6875 | pathogenic | -2.247 | Highly Destabilizing | 0.998 | D | 0.768 | deleterious | None | None | None | None | N |
| Y/R | 0.5967 | likely_pathogenic | 0.5865 | pathogenic | -1.279 | Destabilizing | 0.995 | D | 0.774 | deleterious | None | None | None | None | N |
| Y/S | 0.4075 | ambiguous | 0.3915 | ambiguous | -2.817 | Highly Destabilizing | 0.994 | D | 0.732 | prob.delet. | N | 0.434201262 | None | None | N |
| Y/T | 0.6813 | likely_pathogenic | 0.6586 | pathogenic | -2.572 | Highly Destabilizing | 0.995 | D | 0.741 | deleterious | None | None | None | None | N |
| Y/V | 0.545 | ambiguous | 0.5395 | ambiguous | -2.177 | Highly Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | N |
| Y/W | 0.4208 | ambiguous | 0.411 | ambiguous | -0.668 | Destabilizing | 1.0 | D | 0.744 | 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.