Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32954 | 99085;99086;99087 | chr2:178539075;178539074;178539073 | chr2:179403802;179403801;179403800 |
| N2AB | 31313 | 94162;94163;94164 | chr2:178539075;178539074;178539073 | chr2:179403802;179403801;179403800 |
| N2A | 30386 | 91381;91382;91383 | chr2:178539075;178539074;178539073 | chr2:179403802;179403801;179403800 |
| N2B | 23889 | 71890;71891;71892 | chr2:178539075;178539074;178539073 | chr2:179403802;179403801;179403800 |
| Novex-1 | 24014 | 72265;72266;72267 | chr2:178539075;178539074;178539073 | chr2:179403802;179403801;179403800 |
| Novex-2 | 24081 | 72466;72467;72468 | chr2:178539075;178539074;178539073 | chr2:179403802;179403801;179403800 |
| 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/I | rs372126622  |
0.08 | 1.0 | N | 0.693 | 0.432 | None | gnomAD-2.1.1 | 4.02E-05 | None | None | None | None | N | None | 1.93523E-04 | 1.15949E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 0 |
| T/I | rs372126622 |
0.08 | 1.0 | N | 0.693 | 0.432 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/I | rs372126622 |
0.08 | 1.0 | N | 0.693 | 0.432 | None | gnomAD-4.0.0 | 4.02813E-05 | None | None | None | None | N | None | 2.6703E-05 | 6.66933E-05 | None | 0 | 0 | None | 0 | 0 | 4.83153E-05 | 2.19578E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1282 | likely_benign | 0.1412 | benign | -0.943 | Destabilizing | 0.999 | D | 0.437 | neutral | N | 0.438175366 | None | None | N |
| T/C | 0.7785 | likely_pathogenic | 0.8019 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/D | 0.718 | likely_pathogenic | 0.7382 | pathogenic | -0.056 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/E | 0.7135 | likely_pathogenic | 0.731 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/F | 0.7942 | likely_pathogenic | 0.8201 | pathogenic | -0.994 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| T/G | 0.3529 | ambiguous | 0.4155 | ambiguous | -1.233 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/H | 0.6316 | likely_pathogenic | 0.67 | pathogenic | -1.161 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/I | 0.7877 | likely_pathogenic | 0.7922 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.495530158 | None | None | N |
| T/K | 0.6599 | likely_pathogenic | 0.6621 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| T/L | 0.3869 | ambiguous | 0.4266 | ambiguous | -0.236 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | N |
| T/M | 0.2652 | likely_benign | 0.2755 | benign | -0.281 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| T/N | 0.2601 | likely_benign | 0.2929 | benign | -0.592 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.468111483 | None | None | N |
| T/P | 0.6596 | likely_pathogenic | 0.7051 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.508035309 | None | None | N |
| T/Q | 0.525 | ambiguous | 0.5435 | ambiguous | -0.555 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| T/R | 0.6217 | likely_pathogenic | 0.618 | pathogenic | -0.257 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/S | 0.1594 | likely_benign | 0.188 | benign | -0.957 | Destabilizing | 0.999 | D | 0.448 | neutral | N | 0.406601665 | None | None | N |
| T/V | 0.5189 | ambiguous | 0.5309 | ambiguous | -0.441 | Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| T/W | 0.9535 | likely_pathogenic | 0.9573 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/Y | 0.794 | likely_pathogenic | 0.813 | pathogenic | -0.697 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | 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.