Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5768 | 17527;17528;17529 | chr2:178731464;178731463;178731462 | chr2:179596191;179596190;179596189 |
| N2AB | 5451 | 16576;16577;16578 | chr2:178731464;178731463;178731462 | chr2:179596191;179596190;179596189 |
| N2A | 4524 | 13795;13796;13797 | chr2:178731464;178731463;178731462 | chr2:179596191;179596190;179596189 |
| 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/G | rs1251438106  |
-0.311 | 0.117 | N | 0.405 | 0.312 | 0.248417906384 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| D/G | rs1251438106 |
-0.311 | 0.117 | N | 0.405 | 0.312 | 0.248417906384 | 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/G | rs1251438106 |
-0.311 | 0.117 | N | 0.405 | 0.312 | 0.248417906384 | gnomAD-4.0.0 | 9.91532E-06 | None | None | None | None | N | None | 1.33494E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18665E-05 | 0 | 1.60133E-05 |
| D/N | rs576904726 |
0.285 | 0.426 | N | 0.325 | 0.15 | None | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | N | None | 1.23998E-04 | 5.66E-05 | None | 0 | 5.14E-05 | None | 9.8E-05 | None | 0 | 6.25E-05 | 0 |
| D/N | rs576904726 |
0.285 | 0.426 | N | 0.325 | 0.15 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 7.24E-05 | 1.96515E-04 | 0 | 0 | 1.9305E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/N | rs576904726 |
0.285 | 0.426 | N | 0.325 | 0.15 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| D/N | rs576904726 |
0.285 | 0.426 | N | 0.325 | 0.15 | None | gnomAD-4.0.0 | 6.32078E-05 | None | None | None | None | N | None | 1.19994E-04 | 1.16709E-04 | None | 0 | 1.33845E-04 | None | 3.12451E-05 | 0 | 6.10277E-05 | 3.29395E-05 | 4.80231E-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 | 0.0995 | likely_benign | 0.0927 | benign | -0.269 | Destabilizing | 0.027 | N | 0.367 | neutral | N | 0.442282824 | None | None | N |
| D/C | 0.4014 | ambiguous | 0.3542 | ambiguous | -0.01 | Destabilizing | 0.001 | N | 0.393 | neutral | None | None | None | None | N |
| D/E | 0.0878 | likely_benign | 0.0823 | benign | -0.284 | Destabilizing | None | N | 0.144 | neutral | N | 0.409650331 | None | None | N |
| D/F | 0.3706 | ambiguous | 0.349 | ambiguous | -0.193 | Destabilizing | 0.38 | N | 0.375 | neutral | None | None | None | None | N |
| D/G | 0.1138 | likely_benign | 0.1111 | benign | -0.461 | Destabilizing | 0.117 | N | 0.405 | neutral | N | 0.445381844 | None | None | N |
| D/H | 0.1512 | likely_benign | 0.1415 | benign | 0.022 | Stabilizing | 0.001 | N | 0.167 | neutral | N | 0.457233634 | None | None | N |
| D/I | 0.1795 | likely_benign | 0.1574 | benign | 0.189 | Stabilizing | 0.081 | N | 0.393 | neutral | None | None | None | None | N |
| D/K | 0.1544 | likely_benign | 0.13 | benign | 0.315 | Stabilizing | 0.081 | N | 0.395 | neutral | None | None | None | None | N |
| D/L | 0.222 | likely_benign | 0.1998 | benign | 0.189 | Stabilizing | 0.001 | N | 0.295 | neutral | None | None | None | None | N |
| D/M | 0.3373 | likely_benign | 0.3141 | benign | 0.269 | Stabilizing | 0.38 | N | 0.345 | neutral | None | None | None | None | N |
| D/N | 0.076 | likely_benign | 0.0744 | benign | -0.013 | Destabilizing | 0.426 | N | 0.325 | neutral | N | 0.435164851 | None | None | N |
| D/P | 0.7028 | likely_pathogenic | 0.6741 | pathogenic | 0.058 | Stabilizing | 0.555 | D | 0.402 | neutral | None | None | None | None | N |
| D/Q | 0.1558 | likely_benign | 0.1399 | benign | 0.029 | Stabilizing | 0.081 | N | 0.37 | neutral | None | None | None | None | N |
| D/R | 0.1874 | likely_benign | 0.1641 | benign | 0.496 | Stabilizing | 0.235 | N | 0.376 | neutral | None | None | None | None | N |
| D/S | 0.0825 | likely_benign | 0.0829 | benign | -0.109 | Destabilizing | 0.081 | N | 0.325 | neutral | None | None | None | None | N |
| D/T | 0.122 | likely_benign | 0.1132 | benign | 0.043 | Stabilizing | 0.149 | N | 0.385 | neutral | None | None | None | None | N |
| D/V | 0.1111 | likely_benign | 0.0978 | benign | 0.058 | Stabilizing | 0.062 | N | 0.403 | neutral | N | 0.457060276 | None | None | N |
| D/W | 0.7088 | likely_pathogenic | 0.6886 | pathogenic | -0.063 | Destabilizing | 0.935 | D | 0.389 | neutral | None | None | None | None | N |
| D/Y | 0.1507 | likely_benign | 0.1403 | benign | 0.042 | Stabilizing | 0.541 | D | 0.377 | neutral | N | 0.497984178 | 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.