Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19660 | 59203;59204;59205 | chr2:178593230;178593229;178593228 | chr2:179457957;179457956;179457955 |
| N2AB | 18019 | 54280;54281;54282 | chr2:178593230;178593229;178593228 | chr2:179457957;179457956;179457955 |
| N2A | 17092 | 51499;51500;51501 | chr2:178593230;178593229;178593228 | chr2:179457957;179457956;179457955 |
| N2B | 10595 | 32008;32009;32010 | chr2:178593230;178593229;178593228 | chr2:179457957;179457956;179457955 |
| Novex-1 | 10720 | 32383;32384;32385 | chr2:178593230;178593229;178593228 | chr2:179457957;179457956;179457955 |
| Novex-2 | 10787 | 32584;32585;32586 | chr2:178593230;178593229;178593228 | chr2:179457957;179457956;179457955 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs762554922  |
-0.51 | 0.901 | N | 0.513 | 0.23 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/M | rs762554922 |
-0.51 | 0.901 | N | 0.513 | 0.23 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 4.77555E-04 |
| I/M | rs762554922 |
-0.51 | 0.901 | N | 0.513 | 0.23 | None | gnomAD-4.0.0 | 1.42106E-05 | None | None | None | None | I | None | 1.74734E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44599E-05 | 0 | 3.40229E-05 |
| I/T | rs759613472 |
None | 0.722 | N | 0.543 | 0.335 | 0.485991781493 | gnomAD-4.0.0 | 1.59203E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8594E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2561 | likely_benign | 0.2435 | benign | -0.714 | Destabilizing | 0.633 | D | 0.511 | neutral | None | None | None | None | I |
| I/C | 0.6909 | likely_pathogenic | 0.6711 | pathogenic | -0.698 | Destabilizing | 0.996 | D | 0.58 | neutral | None | None | None | None | I |
| I/D | 0.8763 | likely_pathogenic | 0.8568 | pathogenic | -0.36 | Destabilizing | 0.987 | D | 0.722 | prob.delet. | None | None | None | None | I |
| I/E | 0.7651 | likely_pathogenic | 0.7385 | pathogenic | -0.45 | Destabilizing | 0.961 | D | 0.715 | prob.delet. | None | None | None | None | I |
| I/F | 0.2651 | likely_benign | 0.2372 | benign | -0.694 | Destabilizing | 0.901 | D | 0.499 | neutral | N | 0.510150107 | None | None | I |
| I/G | 0.7793 | likely_pathogenic | 0.7503 | pathogenic | -0.88 | Destabilizing | 0.961 | D | 0.702 | prob.neutral | None | None | None | None | I |
| I/H | 0.7532 | likely_pathogenic | 0.7283 | pathogenic | -0.099 | Destabilizing | 0.996 | D | 0.744 | deleterious | None | None | None | None | I |
| I/K | 0.6372 | likely_pathogenic | 0.6164 | pathogenic | -0.471 | Destabilizing | 0.961 | D | 0.723 | prob.delet. | None | None | None | None | I |
| I/L | 0.1548 | likely_benign | 0.1486 | benign | -0.397 | Destabilizing | 0.19 | N | 0.329 | neutral | N | 0.477037611 | None | None | I |
| I/M | 0.1283 | likely_benign | 0.1222 | benign | -0.465 | Destabilizing | 0.901 | D | 0.513 | neutral | N | 0.473597284 | None | None | I |
| I/N | 0.4893 | ambiguous | 0.4484 | ambiguous | -0.283 | Destabilizing | 0.983 | D | 0.723 | prob.delet. | N | 0.473797867 | None | None | I |
| I/P | 0.9318 | likely_pathogenic | 0.9311 | pathogenic | -0.47 | Destabilizing | 0.987 | D | 0.719 | prob.delet. | None | None | None | None | I |
| I/Q | 0.6887 | likely_pathogenic | 0.6627 | pathogenic | -0.518 | Destabilizing | 0.987 | D | 0.721 | prob.delet. | None | None | None | None | I |
| I/R | 0.4924 | ambiguous | 0.4638 | ambiguous | 0.134 | Stabilizing | 0.961 | D | 0.72 | prob.delet. | None | None | None | None | I |
| I/S | 0.4302 | ambiguous | 0.3879 | ambiguous | -0.722 | Destabilizing | 0.901 | D | 0.616 | neutral | N | 0.510360751 | None | None | I |
| I/T | 0.2019 | likely_benign | 0.1681 | benign | -0.704 | Destabilizing | 0.722 | D | 0.543 | neutral | N | 0.479331275 | None | None | I |
| I/V | 0.0852 | likely_benign | 0.0779 | benign | -0.47 | Destabilizing | 0.003 | N | 0.209 | neutral | N | 0.424568563 | None | None | I |
| I/W | 0.8326 | likely_pathogenic | 0.8174 | pathogenic | -0.696 | Destabilizing | 0.996 | D | 0.769 | deleterious | None | None | None | None | I |
| I/Y | 0.6542 | likely_pathogenic | 0.6456 | pathogenic | -0.462 | Destabilizing | 0.961 | D | 0.552 | 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.