Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15500 | 46723;46724;46725 | chr2:178619819;178619818;178619817 | chr2:179484546;179484545;179484544 |
| N2AB | 13859 | 41800;41801;41802 | chr2:178619819;178619818;178619817 | chr2:179484546;179484545;179484544 |
| N2A | 12932 | 39019;39020;39021 | chr2:178619819;178619818;178619817 | chr2:179484546;179484545;179484544 |
| N2B | 6435 | 19528;19529;19530 | chr2:178619819;178619818;178619817 | chr2:179484546;179484545;179484544 |
| Novex-1 | 6560 | 19903;19904;19905 | chr2:178619819;178619818;178619817 | chr2:179484546;179484545;179484544 |
| Novex-2 | 6627 | 20104;20105;20106 | chr2:178619819;178619818;178619817 | chr2:179484546;179484545;179484544 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | rs529804754  |
-2.182 | None | N | 0.325 | 0.09 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/S | rs529804754 |
-2.182 | None | N | 0.325 | 0.09 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/S | rs529804754 |
-2.182 | None | N | 0.325 | 0.09 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/S | rs529804754 |
-2.182 | None | N | 0.325 | 0.09 | None | gnomAD-4.0.0 | 6.57817E-06 | None | None | None | None | N | None | 2.4079E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.183 | likely_benign | 0.2099 | benign | -2.048 | Highly Destabilizing | 0.007 | N | 0.339 | neutral | None | None | None | None | N |
| L/C | 0.3666 | ambiguous | 0.4961 | ambiguous | -1.091 | Destabilizing | 0.356 | N | 0.416 | neutral | None | None | None | None | N |
| L/D | 0.5847 | likely_pathogenic | 0.5905 | pathogenic | -1.687 | Destabilizing | 0.038 | N | 0.459 | neutral | None | None | None | None | N |
| L/E | 0.1904 | likely_benign | 0.1962 | benign | -1.583 | Destabilizing | None | N | 0.415 | neutral | None | None | None | None | N |
| L/F | 0.0972 | likely_benign | 0.119 | benign | -1.217 | Destabilizing | None | N | 0.183 | neutral | N | 0.418526216 | None | None | N |
| L/G | 0.5344 | ambiguous | 0.6172 | pathogenic | -2.481 | Highly Destabilizing | 0.016 | N | 0.421 | neutral | None | None | None | None | N |
| L/H | 0.1697 | likely_benign | 0.2041 | benign | -1.77 | Destabilizing | 0.214 | N | 0.477 | neutral | None | None | None | None | N |
| L/I | 0.0779 | likely_benign | 0.0891 | benign | -0.864 | Destabilizing | 0.012 | N | 0.386 | neutral | N | 0.418526216 | None | None | N |
| L/K | 0.252 | likely_benign | 0.2765 | benign | -1.512 | Destabilizing | 0.016 | N | 0.437 | neutral | None | None | None | None | N |
| L/M | 0.0763 | likely_benign | 0.0975 | benign | -0.607 | Destabilizing | 0.007 | N | 0.279 | neutral | None | None | None | None | N |
| L/N | 0.3279 | likely_benign | 0.3322 | benign | -1.453 | Destabilizing | 0.038 | N | 0.514 | neutral | None | None | None | None | N |
| L/P | 0.7207 | likely_pathogenic | 0.7633 | pathogenic | -1.232 | Destabilizing | 0.072 | N | 0.551 | neutral | None | None | None | None | N |
| L/Q | 0.1107 | likely_benign | 0.1232 | benign | -1.494 | Destabilizing | 0.038 | N | 0.492 | neutral | None | None | None | None | N |
| L/R | 0.2096 | likely_benign | 0.234 | benign | -1.034 | Destabilizing | 0.072 | N | 0.511 | neutral | None | None | None | None | N |
| L/S | 0.188 | likely_benign | 0.2115 | benign | -2.125 | Highly Destabilizing | None | N | 0.325 | neutral | N | 0.401748046 | None | None | N |
| L/T | 0.1191 | likely_benign | 0.1255 | benign | -1.898 | Destabilizing | 0.016 | N | 0.445 | neutral | None | None | None | None | N |
| L/V | 0.0674 | likely_benign | 0.0781 | benign | -1.232 | Destabilizing | 0.012 | N | 0.353 | neutral | N | 0.402702515 | None | None | N |
| L/W | 0.1821 | likely_benign | 0.2844 | benign | -1.454 | Destabilizing | None | N | 0.333 | neutral | None | None | None | None | N |
| L/Y | 0.2475 | likely_benign | 0.3095 | benign | -1.204 | Destabilizing | None | N | 0.235 | 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.