Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26263 | 79012;79013;79014 | chr2:178567345;178567344;178567343 | chr2:179432072;179432071;179432070 |
| N2AB | 24622 | 74089;74090;74091 | chr2:178567345;178567344;178567343 | chr2:179432072;179432071;179432070 |
| N2A | 23695 | 71308;71309;71310 | chr2:178567345;178567344;178567343 | chr2:179432072;179432071;179432070 |
| N2B | 17198 | 51817;51818;51819 | chr2:178567345;178567344;178567343 | chr2:179432072;179432071;179432070 |
| Novex-1 | 17323 | 52192;52193;52194 | chr2:178567345;178567344;178567343 | chr2:179432072;179432071;179432070 |
| Novex-2 | 17390 | 52393;52394;52395 | chr2:178567345;178567344;178567343 | chr2:179432072;179432071;179432070 |
| 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/E | None | None | 0.309 | N | 0.499 | 0.239 | 0.203808441222 | gnomAD-4.0.0 | 2.07367E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71099E-06 | 0 | 0 |
| Q/H | rs770600641  |
-0.489 | 0.939 | N | 0.56 | 0.417 | 0.303123707472 | gnomAD-2.1.1 | 4.27E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.72E-05 | None | 0 | 0 | 0 |
| Q/H | rs770600641 |
-0.489 | 0.939 | N | 0.56 | 0.417 | 0.303123707472 | gnomAD-4.0.0 | 1.62789E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.50385E-05 | 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 | 0.2211 | likely_benign | 0.2017 | benign | -0.654 | Destabilizing | 0.59 | D | 0.529 | neutral | None | None | None | None | I |
| Q/C | 0.572 | likely_pathogenic | 0.5076 | ambiguous | -0.046 | Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | I |
| Q/D | 0.4169 | ambiguous | 0.3862 | ambiguous | -0.265 | Destabilizing | 0.59 | D | 0.515 | neutral | None | None | None | None | I |
| Q/E | 0.1029 | likely_benign | 0.0983 | benign | -0.164 | Destabilizing | 0.309 | N | 0.499 | neutral | N | 0.493461006 | None | None | I |
| Q/F | 0.67 | likely_pathogenic | 0.611 | pathogenic | -0.326 | Destabilizing | 0.984 | D | 0.632 | neutral | None | None | None | None | I |
| Q/G | 0.3849 | ambiguous | 0.3486 | ambiguous | -1.01 | Destabilizing | 0.742 | D | 0.551 | neutral | None | None | None | None | I |
| Q/H | 0.1884 | likely_benign | 0.158 | benign | -0.773 | Destabilizing | 0.939 | D | 0.56 | neutral | N | 0.485985953 | None | None | I |
| Q/I | 0.297 | likely_benign | 0.2647 | benign | 0.251 | Stabilizing | 0.953 | D | 0.64 | neutral | None | None | None | None | I |
| Q/K | 0.1102 | likely_benign | 0.1062 | benign | -0.229 | Destabilizing | 0.007 | N | 0.224 | neutral | N | 0.489631267 | None | None | I |
| Q/L | 0.136 | likely_benign | 0.1279 | benign | 0.251 | Stabilizing | 0.684 | D | 0.573 | neutral | N | 0.494386513 | None | None | I |
| Q/M | 0.3194 | likely_benign | 0.2954 | benign | 0.622 | Stabilizing | 0.984 | D | 0.555 | neutral | None | None | None | None | I |
| Q/N | 0.2264 | likely_benign | 0.2128 | benign | -0.803 | Destabilizing | 0.037 | N | 0.301 | neutral | None | None | None | None | I |
| Q/P | 0.1678 | likely_benign | 0.1548 | benign | -0.019 | Destabilizing | 0.939 | D | 0.595 | neutral | N | 0.483148342 | None | None | I |
| Q/R | 0.1199 | likely_benign | 0.112 | benign | -0.19 | Destabilizing | 0.521 | D | 0.539 | neutral | N | 0.478070266 | None | None | I |
| Q/S | 0.2308 | likely_benign | 0.2159 | benign | -0.942 | Destabilizing | 0.742 | D | 0.518 | neutral | None | None | None | None | I |
| Q/T | 0.1721 | likely_benign | 0.1626 | benign | -0.637 | Destabilizing | 0.742 | D | 0.539 | neutral | None | None | None | None | I |
| Q/V | 0.2039 | likely_benign | 0.1827 | benign | -0.019 | Destabilizing | 0.91 | D | 0.588 | neutral | None | None | None | None | I |
| Q/W | 0.5937 | likely_pathogenic | 0.539 | ambiguous | -0.166 | Destabilizing | 0.996 | D | 0.673 | neutral | None | None | None | None | I |
| Q/Y | 0.447 | ambiguous | 0.3904 | ambiguous | 0.049 | Stabilizing | 0.984 | D | 0.613 | neutral | None | None | None | None | I |
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.