Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24665 | 74218;74219;74220 | chr2:178572139;178572138;178572137 | chr2:179436866;179436865;179436864 |
| N2AB | 23024 | 69295;69296;69297 | chr2:178572139;178572138;178572137 | chr2:179436866;179436865;179436864 |
| N2A | 22097 | 66514;66515;66516 | chr2:178572139;178572138;178572137 | chr2:179436866;179436865;179436864 |
| N2B | 15600 | 47023;47024;47025 | chr2:178572139;178572138;178572137 | chr2:179436866;179436865;179436864 |
| Novex-1 | 15725 | 47398;47399;47400 | chr2:178572139;178572138;178572137 | chr2:179436866;179436865;179436864 |
| Novex-2 | 15792 | 47599;47600;47601 | chr2:178572139;178572138;178572137 | chr2:179436866;179436865;179436864 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs768288835  |
-0.41 | 0.026 | N | 0.403 | 0.171 | 0.21200892 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs768288835 |
-0.41 | 0.026 | N | 0.403 | 0.171 | 0.21200892 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 2.28739E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/M | rs144398602 |
0.132 | 0.996 | N | 0.579 | 0.269 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| T/M | rs144398602 |
0.132 | 0.996 | N | 0.579 | 0.269 | None | gnomAD-2.1.1 | 1.21839E-04 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 4.13479E-04 | None | 3.27E-05 | None | 0 | 1.88493E-04 | 0 |
| T/M | rs144398602 |
0.132 | 0.996 | N | 0.579 | 0.269 | None | gnomAD-3.1.2 | 1.05209E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.16099E-03 | None | 0 | 0 | 1.47085E-04 | 0 | 0 |
| T/M | rs144398602 |
0.132 | 0.996 | N | 0.579 | 0.269 | None | gnomAD-4.0.0 | 1.01653E-04 | None | None | None | None | N | None | 1.33305E-05 | 0 | None | 0 | 8.94654E-04 | None | 0 | 0 | 9.15582E-05 | 5.49016E-05 | 1.60123E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0583 | likely_benign | 0.0592 | benign | -0.535 | Destabilizing | 0.026 | N | 0.403 | neutral | N | 0.42934245 | None | None | N |
| T/C | 0.3085 | likely_benign | 0.3243 | benign | -0.25 | Destabilizing | 0.993 | D | 0.573 | neutral | None | None | None | None | N |
| T/D | 0.4429 | ambiguous | 0.4407 | ambiguous | -0.179 | Destabilizing | 0.346 | N | 0.462 | neutral | None | None | None | None | N |
| T/E | 0.3017 | likely_benign | 0.3085 | benign | -0.235 | Destabilizing | 0.267 | N | 0.457 | neutral | None | None | None | None | N |
| T/F | 0.2011 | likely_benign | 0.199 | benign | -0.802 | Destabilizing | 0.993 | D | 0.639 | neutral | None | None | None | None | N |
| T/G | 0.2071 | likely_benign | 0.2106 | benign | -0.724 | Destabilizing | 0.816 | D | 0.537 | neutral | None | None | None | None | N |
| T/H | 0.2165 | likely_benign | 0.2202 | benign | -1.005 | Destabilizing | 0.946 | D | 0.625 | neutral | None | None | None | None | N |
| T/I | 0.0935 | likely_benign | 0.0955 | benign | -0.139 | Destabilizing | 0.946 | D | 0.571 | neutral | None | None | None | None | N |
| T/K | 0.163 | likely_benign | 0.1681 | benign | -0.623 | Destabilizing | 0.015 | N | 0.29 | neutral | N | 0.4336522 | None | None | N |
| T/L | 0.0694 | likely_benign | 0.0698 | benign | -0.139 | Destabilizing | 0.711 | D | 0.456 | neutral | None | None | None | None | N |
| T/M | 0.0829 | likely_benign | 0.0835 | benign | 0.169 | Stabilizing | 0.996 | D | 0.579 | neutral | N | 0.49664488 | None | None | N |
| T/N | 0.1118 | likely_benign | 0.113 | benign | -0.369 | Destabilizing | 0.346 | N | 0.423 | neutral | None | None | None | None | N |
| T/P | 0.0795 | likely_benign | 0.0758 | benign | -0.24 | Destabilizing | 0.739 | D | 0.547 | neutral | N | 0.42986253 | None | None | N |
| T/Q | 0.1749 | likely_benign | 0.179 | benign | -0.628 | Destabilizing | 0.043 | N | 0.275 | neutral | None | None | None | None | N |
| T/R | 0.1439 | likely_benign | 0.1442 | benign | -0.275 | Destabilizing | 0.863 | D | 0.455 | neutral | N | 0.43788457 | None | None | N |
| T/S | 0.0969 | likely_benign | 0.1 | benign | -0.59 | Destabilizing | 0.051 | N | 0.427 | neutral | N | 0.4520059 | None | None | N |
| T/V | 0.0758 | likely_benign | 0.078 | benign | -0.24 | Destabilizing | 0.638 | D | 0.382 | neutral | None | None | None | None | N |
| T/W | 0.6082 | likely_pathogenic | 0.6076 | pathogenic | -0.763 | Destabilizing | 0.998 | D | 0.648 | neutral | None | None | None | None | N |
| T/Y | 0.2479 | likely_benign | 0.2549 | benign | -0.531 | Destabilizing | 0.993 | D | 0.643 | 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.