Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30557 | 91894;91895;91896 | chr2:178550169;178550168;178550167 | chr2:179414896;179414895;179414894 |
| N2AB | 28916 | 86971;86972;86973 | chr2:178550169;178550168;178550167 | chr2:179414896;179414895;179414894 |
| N2A | 27989 | 84190;84191;84192 | chr2:178550169;178550168;178550167 | chr2:179414896;179414895;179414894 |
| N2B | 21492 | 64699;64700;64701 | chr2:178550169;178550168;178550167 | chr2:179414896;179414895;179414894 |
| Novex-1 | 21617 | 65074;65075;65076 | chr2:178550169;178550168;178550167 | chr2:179414896;179414895;179414894 |
| Novex-2 | 21684 | 65275;65276;65277 | chr2:178550169;178550168;178550167 | chr2:179414896;179414895;179414894 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | None | None | 0.902 | N | 0.436 | 0.446 | 0.504848970537 | gnomAD-4.0.0 | 6.84218E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99502E-07 | 0 | 0 |
| R/Q | rs745646703  |
0.32 | 0.019 | N | 0.156 | 0.139 | 0.149567049428 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 1.78E-05 | 0 |
| R/Q | rs745646703 |
0.32 | 0.019 | N | 0.156 | 0.139 | 0.149567049428 | 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 |
| R/Q | rs745646703 |
0.32 | 0.019 | N | 0.156 | 0.139 | 0.149567049428 | gnomAD-4.0.0 | 1.79719E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.22826E-05 | None | 3.12471E-05 | 0 | 2.03434E-05 | 1.09794E-05 | 1.60118E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1964 | likely_benign | 0.2378 | benign | 0.04 | Stabilizing | 0.3 | N | 0.238 | neutral | None | None | None | None | I |
| R/C | 0.1247 | likely_benign | 0.1451 | benign | -0.119 | Destabilizing | 0.995 | D | 0.283 | neutral | None | None | None | None | I |
| R/D | 0.4121 | ambiguous | 0.4876 | ambiguous | -0.113 | Destabilizing | 0.704 | D | 0.367 | neutral | None | None | None | None | I |
| R/E | 0.2189 | likely_benign | 0.2547 | benign | -0.049 | Destabilizing | 0.176 | N | 0.2 | neutral | None | None | None | None | I |
| R/F | 0.3537 | ambiguous | 0.4226 | ambiguous | -0.156 | Destabilizing | 0.944 | D | 0.335 | neutral | None | None | None | None | I |
| R/G | 0.1553 | likely_benign | 0.195 | benign | -0.156 | Destabilizing | 0.653 | D | 0.321 | neutral | N | 0.484073395 | None | None | I |
| R/H | 0.0754 | likely_benign | 0.0816 | benign | -0.624 | Destabilizing | 0.944 | D | 0.353 | neutral | None | None | None | None | I |
| R/I | 0.1763 | likely_benign | 0.1974 | benign | 0.522 | Stabilizing | 0.543 | D | 0.401 | neutral | None | None | None | None | I |
| R/K | 0.0732 | likely_benign | 0.0772 | benign | -0.056 | Destabilizing | 0.003 | N | 0.155 | neutral | None | None | None | None | I |
| R/L | 0.156 | likely_benign | 0.1804 | benign | 0.522 | Stabilizing | 0.485 | N | 0.286 | neutral | N | 0.45794571 | None | None | I |
| R/M | 0.1779 | likely_benign | 0.198 | benign | 0.069 | Stabilizing | 0.944 | D | 0.327 | neutral | None | None | None | None | I |
| R/N | 0.3119 | likely_benign | 0.3824 | ambiguous | 0.157 | Stabilizing | 0.704 | D | 0.26 | neutral | None | None | None | None | I |
| R/P | 0.6836 | likely_pathogenic | 0.7547 | pathogenic | 0.382 | Stabilizing | 0.902 | D | 0.436 | neutral | N | 0.520244962 | None | None | I |
| R/Q | 0.0775 | likely_benign | 0.0852 | benign | 0.067 | Stabilizing | 0.019 | N | 0.156 | neutral | N | 0.414808221 | None | None | I |
| R/S | 0.2324 | likely_benign | 0.2879 | benign | -0.159 | Destabilizing | 0.495 | N | 0.293 | neutral | None | None | None | None | I |
| R/T | 0.1202 | likely_benign | 0.1384 | benign | 0.036 | Stabilizing | 0.495 | N | 0.296 | neutral | None | None | None | None | I |
| R/V | 0.1905 | likely_benign | 0.2192 | benign | 0.382 | Stabilizing | 0.013 | N | 0.283 | neutral | None | None | None | None | I |
| R/W | 0.1557 | likely_benign | 0.1816 | benign | -0.219 | Destabilizing | 0.995 | D | 0.293 | neutral | None | None | None | None | I |
| R/Y | 0.2534 | likely_benign | 0.31 | benign | 0.187 | Stabilizing | 0.981 | D | 0.39 | 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.