Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21915 | 65968;65969;65970 | chr2:178583060;178583059;178583058 | chr2:179447787;179447786;179447785 |
| N2AB | 20274 | 61045;61046;61047 | chr2:178583060;178583059;178583058 | chr2:179447787;179447786;179447785 |
| N2A | 19347 | 58264;58265;58266 | chr2:178583060;178583059;178583058 | chr2:179447787;179447786;179447785 |
| N2B | 12850 | 38773;38774;38775 | chr2:178583060;178583059;178583058 | chr2:179447787;179447786;179447785 |
| Novex-1 | 12975 | 39148;39149;39150 | chr2:178583060;178583059;178583058 | chr2:179447787;179447786;179447785 |
| Novex-2 | 13042 | 39349;39350;39351 | chr2:178583060;178583059;178583058 | chr2:179447787;179447786;179447785 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/K | rs62618736  |
0.456 | None | N | 0.097 | 0.141 | None | gnomAD-2.1.1 | 4.62407E-03 | None | None | None | None | N | None | 4.95868E-02 | 1.68822E-03 | None | 0 | 0 | None | 1.97811E-04 | None | 0 | 1.11115E-04 | 1.56472E-03 |
| Q/K | rs62618736 |
0.456 | None | N | 0.097 | 0.141 | None | gnomAD-3.1.2 | 1.38779E-02 | None | None | None | None | N | None | 4.87298E-02 | 4.06131E-03 | 0 | 0 | 1.93798E-04 | None | 0 | 3.16456E-03 | 1.47124E-04 | 2.07211E-04 | 8.12619E-03 |
| Q/K | rs62618736 |
0.456 | None | N | 0.097 | 0.141 | None | 1000 genomes | 1.59744E-02 | None | None | None | None | N | None | 5.75E-02 | 5.8E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| Q/K | rs62618736 |
0.456 | None | N | 0.097 | 0.141 | None | gnomAD-4.0.0 | 2.70174E-03 | None | None | None | None | N | None | 5.11277E-02 | 2.27501E-03 | None | 0 | 2.24709E-05 | None | 0 | 1.98282E-03 | 1.24743E-04 | 1.65242E-04 | 3.38347E-03 |
| Q/R | rs758259657 |
0.578 | 0.003 | N | 0.159 | 0.139 | 0.228597637076 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 2.93E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Q/R | rs758259657 |
0.578 | 0.003 | N | 0.159 | 0.139 | 0.228597637076 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Q/R | rs758259657 |
0.578 | 0.003 | N | 0.159 | 0.139 | 0.228597637076 | gnomAD-4.0.0 | 2.56974E-06 | None | None | None | None | N | None | 0 | 1.70074E-05 | None | 0 | 0 | None | 0 | 0 | 2.39983E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.2114 | likely_benign | 0.2051 | benign | -0.062 | Destabilizing | 0.002 | N | 0.215 | neutral | None | None | None | None | N |
| Q/C | 0.5966 | likely_pathogenic | 0.5603 | ambiguous | 0.109 | Stabilizing | 0.497 | N | 0.261 | neutral | None | None | None | None | N |
| Q/D | 0.3539 | ambiguous | 0.3473 | ambiguous | 0.076 | Stabilizing | 0.018 | N | 0.183 | neutral | None | None | None | None | N |
| Q/E | 0.0949 | likely_benign | 0.097 | benign | 0.036 | Stabilizing | 0.001 | N | 0.157 | neutral | N | 0.416827019 | None | None | N |
| Q/F | 0.6889 | likely_pathogenic | 0.673 | pathogenic | -0.371 | Destabilizing | 0.085 | N | 0.388 | neutral | None | None | None | None | N |
| Q/G | 0.224 | likely_benign | 0.2177 | benign | -0.211 | Destabilizing | 0.008 | N | 0.264 | neutral | None | None | None | None | N |
| Q/H | 0.1908 | likely_benign | 0.1708 | benign | -0.072 | Destabilizing | 0.196 | N | 0.187 | neutral | N | 0.478763699 | None | None | N |
| Q/I | 0.3875 | ambiguous | 0.3767 | ambiguous | 0.235 | Stabilizing | None | N | 0.145 | neutral | None | None | None | None | N |
| Q/K | 0.054 | likely_benign | 0.0523 | benign | 0.117 | Stabilizing | None | N | 0.097 | neutral | N | 0.414384147 | None | None | N |
| Q/L | 0.1526 | likely_benign | 0.1431 | benign | 0.235 | Stabilizing | 0.001 | N | 0.249 | neutral | N | 0.458753787 | None | None | N |
| Q/M | 0.3637 | ambiguous | 0.342 | ambiguous | 0.299 | Stabilizing | 0.085 | N | 0.209 | neutral | None | None | None | None | N |
| Q/N | 0.2397 | likely_benign | 0.2281 | benign | -0.17 | Destabilizing | 0.018 | N | 0.171 | neutral | None | None | None | None | N |
| Q/P | 0.2732 | likely_benign | 0.2592 | benign | 0.163 | Stabilizing | 0.028 | N | 0.267 | neutral | N | 0.472664446 | None | None | N |
| Q/R | 0.0808 | likely_benign | 0.0769 | benign | 0.262 | Stabilizing | 0.003 | N | 0.159 | neutral | N | 0.448728794 | None | None | N |
| Q/S | 0.2058 | likely_benign | 0.1974 | benign | -0.152 | Destabilizing | 0.004 | N | 0.154 | neutral | None | None | None | None | N |
| Q/T | 0.1623 | likely_benign | 0.1556 | benign | -0.051 | Destabilizing | 0.008 | N | 0.212 | neutral | None | None | None | None | N |
| Q/V | 0.2525 | likely_benign | 0.2422 | benign | 0.163 | Stabilizing | None | N | 0.117 | neutral | None | None | None | None | N |
| Q/W | 0.5547 | ambiguous | 0.5421 | ambiguous | -0.416 | Destabilizing | 0.788 | D | 0.234 | neutral | None | None | None | None | N |
| Q/Y | 0.4869 | ambiguous | 0.4753 | ambiguous | -0.128 | Destabilizing | 0.085 | N | 0.323 | neutral | 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.