Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17214 | 51865;51866;51867 | chr2:178609783;178609782;178609781 | chr2:179474510;179474509;179474508 |
| N2AB | 15573 | 46942;46943;46944 | chr2:178609783;178609782;178609781 | chr2:179474510;179474509;179474508 |
| N2A | 14646 | 44161;44162;44163 | chr2:178609783;178609782;178609781 | chr2:179474510;179474509;179474508 |
| N2B | 8149 | 24670;24671;24672 | chr2:178609783;178609782;178609781 | chr2:179474510;179474509;179474508 |
| Novex-1 | 8274 | 25045;25046;25047 | chr2:178609783;178609782;178609781 | chr2:179474510;179474509;179474508 |
| Novex-2 | 8341 | 25246;25247;25248 | chr2:178609783;178609782;178609781 | chr2:179474510;179474509;179474508 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs372443762  |
-0.397 | 0.996 | N | 0.524 | 0.297 | 0.330331372229 | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 2.89855E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40371E-04 |
| E/D | rs372443762 |
-0.397 | 0.996 | N | 0.524 | 0.297 | 0.330331372229 | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | N | None | 2.41581E-04 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/D | rs372443762 |
-0.397 | 0.996 | N | 0.524 | 0.297 | 0.330331372229 | gnomAD-4.0.0 | 6.8453E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99847E-07 | 0 | 0 |
| E/K | rs769926361 |
0.304 | 0.992 | N | 0.599 | 0.306 | 0.485705203746 | gnomAD-4.0.0 | 3.42257E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.80033E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1564 | likely_benign | 0.1616 | benign | -0.448 | Destabilizing | 0.996 | D | 0.575 | neutral | D | 0.52313526 | None | None | N |
| E/C | 0.9276 | likely_pathogenic | 0.9222 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| E/D | 0.3927 | ambiguous | 0.416 | ambiguous | -0.455 | Destabilizing | 0.996 | D | 0.524 | neutral | N | 0.475941142 | None | None | N |
| E/F | 0.9221 | likely_pathogenic | 0.9151 | pathogenic | -0.39 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| E/G | 0.3787 | ambiguous | 0.3545 | ambiguous | -0.668 | Destabilizing | 0.999 | D | 0.573 | neutral | N | 0.493311381 | None | None | N |
| E/H | 0.6974 | likely_pathogenic | 0.7262 | pathogenic | -0.36 | Destabilizing | 0.538 | D | 0.368 | neutral | None | None | None | None | N |
| E/I | 0.4899 | ambiguous | 0.5072 | ambiguous | 0.102 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/K | 0.173 | likely_benign | 0.1924 | benign | 0.184 | Stabilizing | 0.992 | D | 0.599 | neutral | N | 0.472293837 | None | None | N |
| E/L | 0.6221 | likely_pathogenic | 0.6422 | pathogenic | 0.102 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| E/M | 0.6139 | likely_pathogenic | 0.6182 | pathogenic | 0.333 | Stabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| E/N | 0.4957 | ambiguous | 0.5063 | ambiguous | -0.073 | Destabilizing | 0.998 | D | 0.637 | neutral | None | None | None | None | N |
| E/P | 0.3983 | ambiguous | 0.4211 | ambiguous | -0.06 | Destabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | N |
| E/Q | 0.1806 | likely_benign | 0.1843 | benign | -0.041 | Destabilizing | 0.999 | D | 0.635 | neutral | N | 0.468268139 | None | None | N |
| E/R | 0.3111 | likely_benign | 0.3302 | benign | 0.328 | Stabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| E/S | 0.3546 | ambiguous | 0.3626 | ambiguous | -0.257 | Destabilizing | 0.997 | D | 0.609 | neutral | None | None | None | None | N |
| E/T | 0.3528 | ambiguous | 0.3583 | ambiguous | -0.084 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | N |
| E/V | 0.2924 | likely_benign | 0.3083 | benign | -0.06 | Destabilizing | 1.0 | D | 0.621 | neutral | N | 0.468864024 | None | None | N |
| E/W | 0.9759 | likely_pathogenic | 0.9727 | pathogenic | -0.26 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8593 | likely_pathogenic | 0.8498 | pathogenic | -0.156 | Destabilizing | 0.998 | D | 0.601 | 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.