Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25878 | 77857;77858;77859 | chr2:178568500;178568499;178568498 | chr2:179433227;179433226;179433225 |
| N2AB | 24237 | 72934;72935;72936 | chr2:178568500;178568499;178568498 | chr2:179433227;179433226;179433225 |
| N2A | 23310 | 70153;70154;70155 | chr2:178568500;178568499;178568498 | chr2:179433227;179433226;179433225 |
| N2B | 16813 | 50662;50663;50664 | chr2:178568500;178568499;178568498 | chr2:179433227;179433226;179433225 |
| Novex-1 | 16938 | 51037;51038;51039 | chr2:178568500;178568499;178568498 | chr2:179433227;179433226;179433225 |
| Novex-2 | 17005 | 51238;51239;51240 | chr2:178568500;178568499;178568498 | chr2:179433227;179433226;179433225 |
| 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/H | rs765550681  |
-0.561 | 0.939 | N | 0.424 | 0.325 | 0.448099371145 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| Q/H | rs765550681 |
-0.561 | 0.939 | N | 0.424 | 0.325 | 0.448099371145 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Q/H | rs765550681 |
-0.561 | 0.939 | N | 0.424 | 0.325 | 0.448099371145 | gnomAD-4.0.0 | 9.29748E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27162E-05 | 0 | 0 |
| Q/K | None | None | 0.309 | N | 0.377 | 0.165 | 0.190952846119 | gnomAD-4.0.0 | 1.59208E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43324E-05 | 0 |
| Q/R | rs886038876 |
None | 0.007 | N | 0.257 | 0.145 | 0.193865811164 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.2201 | likely_benign | 0.2005 | benign | -0.34 | Destabilizing | 0.373 | N | 0.426 | neutral | None | None | None | None | I |
| Q/C | 0.4603 | ambiguous | 0.4248 | ambiguous | 0.152 | Stabilizing | 0.02 | N | 0.451 | neutral | None | None | None | None | I |
| Q/D | 0.4002 | ambiguous | 0.3727 | ambiguous | -0.047 | Destabilizing | 0.742 | D | 0.34 | neutral | None | None | None | None | I |
| Q/E | 0.082 | likely_benign | 0.0794 | benign | -0.066 | Destabilizing | 0.472 | N | 0.37 | neutral | N | 0.427409372 | None | None | I |
| Q/F | 0.6322 | likely_pathogenic | 0.5903 | pathogenic | -0.454 | Destabilizing | 0.984 | D | 0.555 | neutral | None | None | None | None | I |
| Q/G | 0.2844 | likely_benign | 0.2567 | benign | -0.552 | Destabilizing | 0.742 | D | 0.528 | neutral | None | None | None | None | I |
| Q/H | 0.1882 | likely_benign | 0.1797 | benign | -0.452 | Destabilizing | 0.939 | D | 0.424 | neutral | N | 0.48922841 | None | None | I |
| Q/I | 0.3174 | likely_benign | 0.2849 | benign | 0.139 | Stabilizing | 0.953 | D | 0.562 | neutral | None | None | None | None | I |
| Q/K | 0.0818 | likely_benign | 0.0785 | benign | 0.018 | Stabilizing | 0.309 | N | 0.377 | neutral | N | 0.445648416 | None | None | I |
| Q/L | 0.1329 | likely_benign | 0.1226 | benign | 0.139 | Stabilizing | 0.684 | D | 0.549 | neutral | N | 0.504315505 | None | None | I |
| Q/M | 0.2932 | likely_benign | 0.2658 | benign | 0.469 | Stabilizing | 0.984 | D | 0.422 | neutral | None | None | None | None | I |
| Q/N | 0.2784 | likely_benign | 0.2511 | benign | -0.325 | Destabilizing | 0.742 | D | 0.359 | neutral | None | None | None | None | I |
| Q/P | 0.3737 | ambiguous | 0.3656 | ambiguous | 0.008 | Stabilizing | 0.939 | D | 0.484 | neutral | D | 0.534118337 | None | None | I |
| Q/R | 0.0971 | likely_benign | 0.0959 | benign | 0.187 | Stabilizing | 0.007 | N | 0.257 | neutral | N | 0.491596924 | None | None | I |
| Q/S | 0.2097 | likely_benign | 0.1922 | benign | -0.348 | Destabilizing | 0.045 | N | 0.136 | neutral | None | None | None | None | I |
| Q/T | 0.1471 | likely_benign | 0.1332 | benign | -0.205 | Destabilizing | 0.59 | D | 0.455 | neutral | None | None | None | None | I |
| Q/V | 0.1933 | likely_benign | 0.1741 | benign | 0.008 | Stabilizing | 0.742 | D | 0.56 | neutral | None | None | None | None | I |
| Q/W | 0.5015 | ambiguous | 0.4716 | ambiguous | -0.376 | Destabilizing | 0.996 | D | 0.563 | neutral | None | None | None | None | I |
| Q/Y | 0.4322 | ambiguous | 0.4005 | ambiguous | -0.144 | Destabilizing | 0.984 | D | 0.495 | 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.