Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8466 | 25621;25622;25623 | chr2:178717338;178717337;178717336 | chr2:179582065;179582064;179582063 |
| N2AB | 8149 | 24670;24671;24672 | chr2:178717338;178717337;178717336 | chr2:179582065;179582064;179582063 |
| N2A | 7222 | 21889;21890;21891 | chr2:178717338;178717337;178717336 | chr2:179582065;179582064;179582063 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs72648986  |
-0.092 | 0.001 | N | 0.111 | 0.11 | 0.148003135375 | gnomAD-2.1.1 | 1.10534E-02 | None | None | None | None | N | None | 7.56824E-02 | 4.8409E-03 | None | 6.58404E-03 | 1.0248E-04 | None | 2.19823E-02 | None | 4E-05 | 2.30022E-03 | 7.73994E-03 |
| D/E | rs72648986 |
-0.092 | 0.001 | N | 0.111 | 0.11 | 0.148003135375 | gnomAD-3.1.2 | 2.39604E-02 | None | None | None | None | N | None | 7.56903E-02 | 1.12595E-02 | 0 | 7.20046E-03 | 0 | None | 0 | 9.49367E-03 | 2.07274E-03 | 2.40664E-02 | 2.53104E-02 |
| D/E | rs72648986 |
-0.092 | 0.001 | N | 0.111 | 0.11 | 0.148003135375 | 1000 genomes | 2.8754E-02 | None | None | None | None | N | None | 8.09E-02 | 1.01E-02 | None | None | 0 | 3E-03 | None | None | None | 2.76E-02 | None |
| D/E | rs72648986 |
-0.092 | 0.001 | N | 0.111 | 0.11 | 0.148003135375 | gnomAD-4.0.0 | 6.60199E-03 | None | None | None | None | N | None | 7.56533E-02 | 6.89862E-03 | None | 7.67151E-03 | 1.78269E-04 | None | 6.24824E-05 | 8.25628E-03 | 1.45907E-03 | 2.13269E-02 | 9.81428E-03 |
| D/G | rs773229351 |
-0.429 | 0.053 | N | 0.327 | 0.127 | 0.233150807113 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.82E-06 | 0 |
| D/G | rs773229351 |
-0.429 | 0.053 | N | 0.327 | 0.127 | 0.233150807113 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs773229351 |
-0.429 | 0.053 | N | 0.327 | 0.127 | 0.233150807113 | gnomAD-4.0.0 | 5.12636E-06 | None | None | None | None | N | None | 3.38295E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.789E-06 | 0 | 0 |
| D/H | rs372994306 |
0.256 | 0.783 | N | 0.347 | 0.183 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.23E-05 | 0 |
| D/H | rs372994306 |
0.256 | 0.783 | N | 0.347 | 0.183 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/H | rs372994306 |
0.256 | 0.783 | N | 0.347 | 0.183 | None | gnomAD-4.0.0 | 2.29344E-05 | None | None | None | None | N | None | 1.33529E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.96744E-05 | 0 | 1.60159E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.173 | likely_benign | 0.1565 | benign | -0.281 | Destabilizing | 0.072 | N | 0.299 | neutral | N | 0.469853428 | None | None | N |
| D/C | 0.713 | likely_pathogenic | 0.6579 | pathogenic | -0.074 | Destabilizing | 0.922 | D | 0.313 | neutral | None | None | None | None | N |
| D/E | 0.1665 | likely_benign | 0.165 | benign | -0.301 | Destabilizing | 0.001 | N | 0.111 | neutral | N | 0.415594868 | None | None | N |
| D/F | 0.5099 | ambiguous | 0.4763 | ambiguous | -0.073 | Destabilizing | 0.927 | D | 0.342 | neutral | None | None | None | None | N |
| D/G | 0.1775 | likely_benign | 0.1687 | benign | -0.5 | Destabilizing | 0.053 | N | 0.327 | neutral | N | 0.494135797 | None | None | N |
| D/H | 0.2571 | likely_benign | 0.231 | benign | 0.113 | Stabilizing | 0.783 | D | 0.347 | neutral | N | 0.480571854 | None | None | N |
| D/I | 0.3323 | likely_benign | 0.299 | benign | 0.253 | Stabilizing | 0.473 | N | 0.415 | neutral | None | None | None | None | N |
| D/K | 0.4011 | ambiguous | 0.3452 | ambiguous | 0.348 | Stabilizing | 0.023 | N | 0.198 | neutral | None | None | None | None | N |
| D/L | 0.3319 | likely_benign | 0.3019 | benign | 0.253 | Stabilizing | 0.473 | N | 0.383 | neutral | None | None | None | None | N |
| D/M | 0.5871 | likely_pathogenic | 0.5452 | ambiguous | 0.304 | Stabilizing | 0.827 | D | 0.327 | neutral | None | None | None | None | N |
| D/N | 0.0968 | likely_benign | 0.0911 | benign | -0.104 | Destabilizing | None | N | 0.094 | neutral | N | 0.435703569 | None | None | N |
| D/P | 0.6125 | likely_pathogenic | 0.5451 | ambiguous | 0.098 | Stabilizing | 0.067 | N | 0.415 | neutral | None | None | None | None | N |
| D/Q | 0.304 | likely_benign | 0.2717 | benign | -0.046 | Destabilizing | 0.401 | N | 0.308 | neutral | None | None | None | None | N |
| D/R | 0.3972 | ambiguous | 0.3565 | ambiguous | 0.551 | Stabilizing | 0.023 | N | 0.217 | neutral | None | None | None | None | N |
| D/S | 0.1188 | likely_benign | 0.1092 | benign | -0.194 | Destabilizing | 0.019 | N | 0.148 | neutral | None | None | None | None | N |
| D/T | 0.2322 | likely_benign | 0.2016 | benign | -0.015 | Destabilizing | 0.044 | N | 0.335 | neutral | None | None | None | None | N |
| D/V | 0.1982 | likely_benign | 0.1779 | benign | 0.098 | Stabilizing | 0.003 | N | 0.252 | neutral | N | 0.43092968 | None | None | N |
| D/W | 0.8718 | likely_pathogenic | 0.8415 | pathogenic | 0.101 | Stabilizing | 0.993 | D | 0.416 | neutral | None | None | None | None | N |
| D/Y | 0.2053 | likely_benign | 0.1949 | benign | 0.179 | Stabilizing | 0.967 | D | 0.342 | neutral | N | 0.485054953 | 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.