Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8891 | 26896;26897;26898 | chr2:178713987;178713986;178713985 | chr2:179578714;179578713;179578712 |
| N2AB | 8574 | 25945;25946;25947 | chr2:178713987;178713986;178713985 | chr2:179578714;179578713;179578712 |
| N2A | 7647 | 23164;23165;23166 | chr2:178713987;178713986;178713985 | chr2:179578714;179578713;179578712 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | None | None | 0.295 | N | 0.271 | 0.151 | 0.181679512989 | gnomAD-4.0.0 | 1.59163E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43316E-05 | 0 |
| N/K | None | None | 0.012 | N | 0.187 | 0.145 | 0.0297737177859 | gnomAD-4.0.0 | 6.84285E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99535E-07 | 0 | 0 |
| N/S | rs146057575  |
-0.235 | None | N | 0.077 | 0.089 | None | gnomAD-2.1.1 | 3.46196E-04 | None | None | None | None | N | None | 2.89304E-04 | 7.36836E-04 | None | 3.86623E-04 | 0 | None | 4.90773E-04 | None | 0 | 2.96426E-04 | 9.83422E-04 |
| N/S | rs146057575 |
-0.235 | None | N | 0.077 | 0.089 | None | gnomAD-3.1.2 | 3.28528E-04 | None | None | None | None | N | None | 1.44711E-04 | 1.17863E-03 | 0 | 0 | 0 | None | 0 | 1.58228E-02 | 2.35177E-04 | 2.07039E-04 | 1.91205E-03 |
| N/S | rs146057575 |
-0.235 | None | N | 0.077 | 0.089 | None | 1000 genomes | 1.59744E-03 | None | None | None | None | N | None | 5.3E-03 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| N/S | rs146057575 |
-0.235 | None | N | 0.077 | 0.089 | None | gnomAD-4.0.0 | 2.62133E-04 | None | None | None | None | N | None | 3.59789E-04 | 7.66794E-04 | None | 2.36486E-04 | 0 | None | 0 | 1.45167E-02 | 1.57667E-04 | 4.17298E-04 | 4.96254E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1768 | likely_benign | 0.1993 | benign | -0.483 | Destabilizing | None | N | 0.116 | neutral | None | None | None | None | N |
| N/C | 0.2808 | likely_benign | 0.3168 | benign | 0.309 | Stabilizing | 0.356 | N | 0.387 | neutral | None | None | None | None | N |
| N/D | 0.0964 | likely_benign | 0.1006 | benign | 0.017 | Stabilizing | 0.012 | N | 0.168 | neutral | N | 0.448359782 | None | None | N |
| N/E | 0.2808 | likely_benign | 0.3207 | benign | -0.007 | Destabilizing | 0.016 | N | 0.201 | neutral | None | None | None | None | N |
| N/F | 0.5309 | ambiguous | 0.5571 | ambiguous | -0.768 | Destabilizing | 0.214 | N | 0.457 | neutral | None | None | None | None | N |
| N/G | 0.18 | likely_benign | 0.2016 | benign | -0.679 | Destabilizing | 0.007 | N | 0.172 | neutral | None | None | None | None | N |
| N/H | 0.0841 | likely_benign | 0.0962 | benign | -0.662 | Destabilizing | 0.295 | N | 0.271 | neutral | N | 0.488939755 | None | None | N |
| N/I | 0.3996 | ambiguous | 0.4226 | ambiguous | -0.049 | Destabilizing | 0.029 | N | 0.384 | neutral | N | 0.484804415 | None | None | N |
| N/K | 0.1895 | likely_benign | 0.2301 | benign | 0.078 | Stabilizing | 0.012 | N | 0.187 | neutral | N | 0.469255129 | None | None | N |
| N/L | 0.2779 | likely_benign | 0.306 | benign | -0.049 | Destabilizing | 0.002 | N | 0.265 | neutral | None | None | None | None | N |
| N/M | 0.3369 | likely_benign | 0.3804 | ambiguous | 0.436 | Stabilizing | 0.001 | N | 0.165 | neutral | None | None | None | None | N |
| N/P | 0.6629 | likely_pathogenic | 0.6625 | pathogenic | -0.166 | Destabilizing | 0.072 | N | 0.398 | neutral | None | None | None | None | N |
| N/Q | 0.2186 | likely_benign | 0.2623 | benign | -0.489 | Destabilizing | 0.072 | N | 0.184 | neutral | None | None | None | None | N |
| N/R | 0.2087 | likely_benign | 0.2495 | benign | 0.17 | Stabilizing | 0.072 | N | 0.181 | neutral | None | None | None | None | N |
| N/S | 0.0699 | likely_benign | 0.0713 | benign | -0.263 | Destabilizing | None | N | 0.077 | neutral | N | 0.403088852 | None | None | N |
| N/T | 0.1344 | likely_benign | 0.1408 | benign | -0.133 | Destabilizing | 0.012 | N | 0.189 | neutral | N | 0.507525516 | None | None | N |
| N/V | 0.3487 | ambiguous | 0.3853 | ambiguous | -0.166 | Destabilizing | 0.016 | N | 0.293 | neutral | None | None | None | None | N |
| N/W | 0.6546 | likely_pathogenic | 0.7103 | pathogenic | -0.674 | Destabilizing | 0.864 | D | 0.373 | neutral | None | None | None | None | N |
| N/Y | 0.1635 | likely_benign | 0.1772 | benign | -0.435 | Destabilizing | 0.295 | N | 0.441 | neutral | N | 0.461584825 | 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.