Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35744 | 107455;107456;107457 | chr2:178528421;178528420;178528419 | chr2:179393148;179393147;179393146 |
| N2AB | 34103 | 102532;102533;102534 | chr2:178528421;178528420;178528419 | chr2:179393148;179393147;179393146 |
| N2A | 33176 | 99751;99752;99753 | chr2:178528421;178528420;178528419 | chr2:179393148;179393147;179393146 |
| N2B | 26679 | 80260;80261;80262 | chr2:178528421;178528420;178528419 | chr2:179393148;179393147;179393146 |
| Novex-1 | 26804 | 80635;80636;80637 | chr2:178528421;178528420;178528419 | chr2:179393148;179393147;179393146 |
| Novex-2 | 26871 | 80836;80837;80838 | chr2:178528421;178528420;178528419 | chr2:179393148;179393147;179393146 |
| 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/L | rs142336788  |
None | None | N | 0.139 | 0.074 | 0.0551355673512 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs142336788 |
None | None | N | 0.139 | 0.074 | 0.0551355673512 | gnomAD-4.0.0 | 6.57065E-06 | None | None | None | None | N | None | 2.41278E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 0.012 | N | 0.335 | 0.321 | 0.508755544265 | gnomAD-4.0.0 | 6.84708E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52003E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs142336788 |
0.114 | None | N | 0.159 | 0.053 | None | gnomAD-2.1.1 | 7.91E-05 | None | None | None | None | N | None | 6.62471E-04 | 2.86E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.92E-05 | 0 |
| I/V | rs142336788 |
0.114 | None | N | 0.159 | 0.053 | None | gnomAD-3.1.2 | 1.90549E-04 | None | None | None | None | N | None | 6.99706E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs142336788 |
0.114 | None | N | 0.159 | 0.053 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs142336788 |
0.114 | None | N | 0.159 | 0.053 | None | gnomAD-4.0.0 | 1.04168E-04 | None | None | None | None | N | None | 7.20192E-04 | 1.67235E-05 | None | 3.38226E-05 | 2.22896E-05 | None | 0 | 0 | 8.90155E-05 | 2.20814E-05 | 6.40594E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2219 | likely_benign | 0.1908 | benign | -0.484 | Destabilizing | None | N | 0.156 | neutral | None | None | None | None | N |
| I/C | 0.6923 | likely_pathogenic | 0.624 | pathogenic | -0.82 | Destabilizing | 0.356 | N | 0.317 | neutral | None | None | None | None | N |
| I/D | 0.5232 | ambiguous | 0.451 | ambiguous | 0.281 | Stabilizing | 0.356 | N | 0.369 | neutral | None | None | None | None | N |
| I/E | 0.4626 | ambiguous | 0.3921 | ambiguous | 0.215 | Stabilizing | 0.136 | N | 0.38 | neutral | None | None | None | None | N |
| I/F | 0.1535 | likely_benign | 0.1351 | benign | -0.446 | Destabilizing | 0.055 | N | 0.237 | neutral | N | 0.434164773 | None | None | N |
| I/G | 0.4876 | ambiguous | 0.4235 | ambiguous | -0.634 | Destabilizing | 0.072 | N | 0.385 | neutral | None | None | None | None | N |
| I/H | 0.4709 | ambiguous | 0.3975 | ambiguous | -0.006 | Destabilizing | 0.864 | D | 0.297 | neutral | None | None | None | None | N |
| I/K | 0.3485 | ambiguous | 0.2818 | benign | -0.26 | Destabilizing | 0.136 | N | 0.389 | neutral | None | None | None | None | N |
| I/L | 0.1049 | likely_benign | 0.0935 | benign | -0.207 | Destabilizing | None | N | 0.139 | neutral | N | 0.404996659 | None | None | N |
| I/M | 0.1197 | likely_benign | 0.1116 | benign | -0.455 | Destabilizing | 0.171 | N | 0.28 | neutral | N | 0.423390419 | None | None | N |
| I/N | 0.2039 | likely_benign | 0.1792 | benign | -0.195 | Destabilizing | 0.56 | D | 0.347 | neutral | N | 0.400358844 | None | None | N |
| I/P | 0.4397 | ambiguous | 0.3711 | ambiguous | -0.268 | Destabilizing | 0.356 | N | 0.359 | neutral | None | None | None | None | N |
| I/Q | 0.3992 | ambiguous | 0.3303 | benign | -0.304 | Destabilizing | 0.628 | D | 0.325 | neutral | None | None | None | None | N |
| I/R | 0.2698 | likely_benign | 0.2219 | benign | 0.121 | Stabilizing | 0.356 | N | 0.351 | neutral | None | None | None | None | N |
| I/S | 0.2095 | likely_benign | 0.1886 | benign | -0.686 | Destabilizing | 0.029 | N | 0.345 | neutral | N | 0.366974202 | None | None | N |
| I/T | 0.1841 | likely_benign | 0.162 | benign | -0.637 | Destabilizing | 0.012 | N | 0.335 | neutral | N | 0.381965084 | None | None | N |
| I/V | 0.0652 | likely_benign | 0.0641 | benign | -0.268 | Destabilizing | None | N | 0.159 | neutral | N | 0.405458019 | None | None | N |
| I/W | 0.7856 | likely_pathogenic | 0.7177 | pathogenic | -0.486 | Destabilizing | 0.864 | D | 0.308 | neutral | None | None | None | None | N |
| I/Y | 0.4606 | ambiguous | 0.4048 | ambiguous | -0.239 | Destabilizing | 0.356 | N | 0.345 | 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.