Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24599 | 74020;74021;74022 | chr2:178572337;178572336;178572335 | chr2:179437064;179437063;179437062 |
| N2AB | 22958 | 69097;69098;69099 | chr2:178572337;178572336;178572335 | chr2:179437064;179437063;179437062 |
| N2A | 22031 | 66316;66317;66318 | chr2:178572337;178572336;178572335 | chr2:179437064;179437063;179437062 |
| N2B | 15534 | 46825;46826;46827 | chr2:178572337;178572336;178572335 | chr2:179437064;179437063;179437062 |
| Novex-1 | 15659 | 47200;47201;47202 | chr2:178572337;178572336;178572335 | chr2:179437064;179437063;179437062 |
| Novex-2 | 15726 | 47401;47402;47403 | chr2:178572337;178572336;178572335 | chr2:179437064;179437063;179437062 |
| 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/H | rs754578013  |
-0.464 | 0.938 | N | 0.53 | 0.412 | 0.255270683199 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| Y/N | rs754578013 |
-0.204 | 0.981 | N | 0.671 | 0.459 | 0.43912465853 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/N | rs754578013 |
-0.204 | 0.981 | N | 0.671 | 0.459 | 0.43912465853 | gnomAD-4.0.0 | 1.59616E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43349E-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 | 0.9375 | likely_pathogenic | 0.8747 | pathogenic | -0.895 | Destabilizing | 0.609 | D | 0.618 | neutral | None | None | None | None | I |
| Y/C | 0.5058 | ambiguous | 0.4213 | ambiguous | -0.036 | Destabilizing | 0.995 | D | 0.699 | prob.neutral | D | 0.523193975 | None | None | I |
| Y/D | 0.9448 | likely_pathogenic | 0.891 | pathogenic | 0.874 | Stabilizing | 0.981 | D | 0.678 | prob.neutral | N | 0.48939368 | None | None | I |
| Y/E | 0.9766 | likely_pathogenic | 0.9564 | pathogenic | 0.856 | Stabilizing | 0.957 | D | 0.655 | neutral | None | None | None | None | I |
| Y/F | 0.103 | likely_benign | 0.1101 | benign | -0.506 | Destabilizing | 0.001 | N | 0.38 | neutral | N | 0.459990646 | None | None | I |
| Y/G | 0.938 | likely_pathogenic | 0.8871 | pathogenic | -1.088 | Destabilizing | 0.957 | D | 0.613 | neutral | None | None | None | None | I |
| Y/H | 0.6182 | likely_pathogenic | 0.5272 | ambiguous | 0.114 | Stabilizing | 0.938 | D | 0.53 | neutral | N | 0.494313863 | None | None | I |
| Y/I | 0.7491 | likely_pathogenic | 0.7006 | pathogenic | -0.408 | Destabilizing | 0.057 | N | 0.62 | neutral | None | None | None | None | I |
| Y/K | 0.978 | likely_pathogenic | 0.9632 | pathogenic | 0.127 | Stabilizing | 0.728 | D | 0.656 | neutral | None | None | None | None | I |
| Y/L | 0.7595 | likely_pathogenic | 0.7111 | pathogenic | -0.408 | Destabilizing | 0.024 | N | 0.585 | neutral | None | None | None | None | I |
| Y/M | 0.8254 | likely_pathogenic | 0.7842 | pathogenic | -0.149 | Destabilizing | 0.869 | D | 0.597 | neutral | None | None | None | None | I |
| Y/N | 0.665 | likely_pathogenic | 0.5399 | ambiguous | -0.028 | Destabilizing | 0.981 | D | 0.671 | neutral | N | 0.510590037 | None | None | I |
| Y/P | 0.9968 | likely_pathogenic | 0.9936 | pathogenic | -0.55 | Destabilizing | 0.985 | D | 0.683 | prob.neutral | None | None | None | None | I |
| Y/Q | 0.9561 | likely_pathogenic | 0.9207 | pathogenic | -0.037 | Destabilizing | 0.953 | D | 0.601 | neutral | None | None | None | None | I |
| Y/R | 0.9557 | likely_pathogenic | 0.9307 | pathogenic | 0.49 | Stabilizing | 0.902 | D | 0.673 | neutral | None | None | None | None | I |
| Y/S | 0.8888 | likely_pathogenic | 0.8083 | pathogenic | -0.54 | Destabilizing | 0.943 | D | 0.611 | neutral | N | 0.470657541 | None | None | I |
| Y/T | 0.9408 | likely_pathogenic | 0.9041 | pathogenic | -0.468 | Destabilizing | 0.916 | D | 0.587 | neutral | None | None | None | None | I |
| Y/V | 0.7143 | likely_pathogenic | 0.6636 | pathogenic | -0.55 | Destabilizing | 0.01 | N | 0.447 | neutral | None | None | None | None | I |
| Y/W | 0.6432 | likely_pathogenic | 0.5991 | pathogenic | -0.542 | Destabilizing | 0.993 | D | 0.521 | neutral | 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.