Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18511 | 55756;55757;55758 | chr2:178601466;178601465;178601464 | chr2:179466193;179466192;179466191 |
| N2AB | 16870 | 50833;50834;50835 | chr2:178601466;178601465;178601464 | chr2:179466193;179466192;179466191 |
| N2A | 15943 | 48052;48053;48054 | chr2:178601466;178601465;178601464 | chr2:179466193;179466192;179466191 |
| N2B | 9446 | 28561;28562;28563 | chr2:178601466;178601465;178601464 | chr2:179466193;179466192;179466191 |
| Novex-1 | 9571 | 28936;28937;28938 | chr2:178601466;178601465;178601464 | chr2:179466193;179466192;179466191 |
| Novex-2 | 9638 | 29137;29138;29139 | chr2:178601466;178601465;178601464 | chr2:179466193;179466192;179466191 |
| 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/F | rs757290658  |
-1.841 | 1.0 | N | 0.829 | 0.537 | 0.500426043041 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| I/F | rs757290658 |
-1.841 | 1.0 | N | 0.829 | 0.537 | 0.500426043041 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/F | rs757290658 |
-1.841 | 1.0 | N | 0.829 | 0.537 | 0.500426043041 | gnomAD-4.0.0 | 1.31563E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.94256E-05 | 0 | 0 |
| I/S | rs2053434343 |
None | 1.0 | D | 0.845 | 0.615 | 0.895340695038 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/S | rs2053434343 |
None | 1.0 | D | 0.845 | 0.615 | 0.895340695038 | gnomAD-4.0.0 | 6.58172E-06 | None | None | None | None | I | None | 0 | 6.56168E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.993 | N | 0.397 | 0.234 | 0.508934680445 | gnomAD-4.0.0 | 1.59287E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43394E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9785 | likely_pathogenic | 0.989 | pathogenic | -2.464 | Highly Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | I |
| I/C | 0.961 | likely_pathogenic | 0.9798 | pathogenic | -1.411 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| I/D | 0.998 | likely_pathogenic | 0.9992 | pathogenic | -2.388 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| I/E | 0.9911 | likely_pathogenic | 0.9953 | pathogenic | -2.301 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | I |
| I/F | 0.9117 | likely_pathogenic | 0.9467 | pathogenic | -1.681 | Destabilizing | 1.0 | D | 0.829 | deleterious | N | 0.518282626 | None | None | I |
| I/G | 0.9928 | likely_pathogenic | 0.9973 | pathogenic | -2.892 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| I/H | 0.9935 | likely_pathogenic | 0.9975 | pathogenic | -2.187 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| I/K | 0.9848 | likely_pathogenic | 0.9914 | pathogenic | -1.827 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| I/L | 0.4098 | ambiguous | 0.5224 | ambiguous | -1.282 | Destabilizing | 0.993 | D | 0.416 | neutral | D | 0.526354497 | None | None | I |
| I/M | 0.5352 | ambiguous | 0.6698 | pathogenic | -0.858 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.532173826 | None | None | I |
| I/N | 0.9367 | likely_pathogenic | 0.9796 | pathogenic | -1.746 | Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.533187784 | None | None | I |
| I/P | 0.954 | likely_pathogenic | 0.9685 | pathogenic | -1.652 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| I/Q | 0.9854 | likely_pathogenic | 0.9928 | pathogenic | -1.844 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| I/R | 0.9811 | likely_pathogenic | 0.9897 | pathogenic | -1.236 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| I/S | 0.9754 | likely_pathogenic | 0.9894 | pathogenic | -2.383 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.532427316 | None | None | I |
| I/T | 0.9579 | likely_pathogenic | 0.9758 | pathogenic | -2.178 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | N | 0.514323061 | None | None | I |
| I/V | 0.1574 | likely_benign | 0.1582 | benign | -1.652 | Destabilizing | 0.993 | D | 0.397 | neutral | N | 0.479427342 | None | None | I |
| I/W | 0.9956 | likely_pathogenic | 0.9981 | pathogenic | -1.918 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| I/Y | 0.9853 | likely_pathogenic | 0.992 | pathogenic | -1.722 | Destabilizing | 1.0 | D | 0.849 | 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.