Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15000 | 45223;45224;45225 | chr2:178621924;178621923;178621922 | chr2:179486651;179486650;179486649 |
| N2AB | 13359 | 40300;40301;40302 | chr2:178621924;178621923;178621922 | chr2:179486651;179486650;179486649 |
| N2A | 12432 | 37519;37520;37521 | chr2:178621924;178621923;178621922 | chr2:179486651;179486650;179486649 |
| N2B | 5935 | 18028;18029;18030 | chr2:178621924;178621923;178621922 | chr2:179486651;179486650;179486649 |
| Novex-1 | 6060 | 18403;18404;18405 | chr2:178621924;178621923;178621922 | chr2:179486651;179486650;179486649 |
| Novex-2 | 6127 | 18604;18605;18606 | chr2:178621924;178621923;178621922 | chr2:179486651;179486650;179486649 |
| 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 | rs886055275  |
None | 0.722 | D | 0.684 | 0.727 | 0.807264362512 | gnomAD-4.0.0 | 1.59515E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03269E-05 |
| I/V | rs775264673 |
-1.719 | 0.001 | D | 0.289 | 0.192 | 0.534719010399 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs775264673 |
-1.719 | 0.001 | D | 0.289 | 0.192 | 0.534719010399 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs775264673 |
-1.719 | 0.001 | D | 0.289 | 0.192 | 0.534719010399 | gnomAD-4.0.0 | 6.57981E-06 | None | None | None | None | N | None | 2.41371E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9689 | likely_pathogenic | 0.9607 | pathogenic | -2.921 | Highly Destabilizing | 0.415 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/C | 0.9732 | likely_pathogenic | 0.9695 | pathogenic | -2.343 | Highly Destabilizing | 0.989 | D | 0.749 | deleterious | None | None | None | None | N |
| I/D | 0.9985 | likely_pathogenic | 0.9979 | pathogenic | -3.731 | Highly Destabilizing | 0.987 | D | 0.811 | deleterious | None | None | None | None | N |
| I/E | 0.9944 | likely_pathogenic | 0.9927 | pathogenic | -3.416 | Highly Destabilizing | 0.961 | D | 0.804 | deleterious | None | None | None | None | N |
| I/F | 0.7338 | likely_pathogenic | 0.7017 | pathogenic | -1.713 | Destabilizing | 0.901 | D | 0.721 | prob.delet. | D | 0.671523742 | None | None | N |
| I/G | 0.9953 | likely_pathogenic | 0.9936 | pathogenic | -3.531 | Highly Destabilizing | 0.961 | D | 0.783 | deleterious | None | None | None | None | N |
| I/H | 0.9929 | likely_pathogenic | 0.9906 | pathogenic | -3.209 | Highly Destabilizing | 0.996 | D | 0.806 | deleterious | None | None | None | None | N |
| I/K | 0.9844 | likely_pathogenic | 0.9802 | pathogenic | -2.306 | Highly Destabilizing | 0.961 | D | 0.803 | deleterious | None | None | None | None | N |
| I/L | 0.3912 | ambiguous | 0.386 | ambiguous | -1.084 | Destabilizing | 0.19 | N | 0.395 | neutral | D | 0.620465158 | None | None | N |
| I/M | 0.3827 | ambiguous | 0.3824 | ambiguous | -1.323 | Destabilizing | 0.901 | D | 0.695 | prob.neutral | D | 0.724929369 | None | None | N |
| I/N | 0.9753 | likely_pathogenic | 0.9704 | pathogenic | -3.005 | Highly Destabilizing | 0.983 | D | 0.815 | deleterious | D | 0.780467561 | None | None | N |
| I/P | 0.9973 | likely_pathogenic | 0.996 | pathogenic | -1.688 | Destabilizing | 0.987 | D | 0.814 | deleterious | None | None | None | None | N |
| I/Q | 0.9873 | likely_pathogenic | 0.9839 | pathogenic | -2.674 | Highly Destabilizing | 0.987 | D | 0.811 | deleterious | None | None | None | None | N |
| I/R | 0.9793 | likely_pathogenic | 0.9722 | pathogenic | -2.269 | Highly Destabilizing | 0.961 | D | 0.814 | deleterious | None | None | None | None | N |
| I/S | 0.9762 | likely_pathogenic | 0.9691 | pathogenic | -3.579 | Highly Destabilizing | 0.901 | D | 0.771 | deleterious | D | 0.780467561 | None | None | N |
| I/T | 0.9625 | likely_pathogenic | 0.9525 | pathogenic | -3.103 | Highly Destabilizing | 0.722 | D | 0.684 | prob.neutral | D | 0.780671918 | None | None | N |
| I/V | 0.1615 | likely_benign | 0.1577 | benign | -1.688 | Destabilizing | 0.001 | N | 0.289 | neutral | D | 0.539303674 | None | None | N |
| I/W | 0.992 | likely_pathogenic | 0.9897 | pathogenic | -2.191 | Highly Destabilizing | 0.996 | D | 0.805 | deleterious | None | None | None | None | N |
| I/Y | 0.9758 | likely_pathogenic | 0.9691 | pathogenic | -1.995 | Destabilizing | 0.961 | D | 0.749 | 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.