Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26099 | 78520;78521;78522 | chr2:178567837;178567836;178567835 | chr2:179432564;179432563;179432562 |
| N2AB | 24458 | 73597;73598;73599 | chr2:178567837;178567836;178567835 | chr2:179432564;179432563;179432562 |
| N2A | 23531 | 70816;70817;70818 | chr2:178567837;178567836;178567835 | chr2:179432564;179432563;179432562 |
| N2B | 17034 | 51325;51326;51327 | chr2:178567837;178567836;178567835 | chr2:179432564;179432563;179432562 |
| Novex-1 | 17159 | 51700;51701;51702 | chr2:178567837;178567836;178567835 | chr2:179432564;179432563;179432562 |
| Novex-2 | 17226 | 51901;51902;51903 | chr2:178567837;178567836;178567835 | chr2:179432564;179432563;179432562 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | rs374376033  |
None | None | N | 0.043 | 0.104 | 0.420570264827 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/L | rs374376033 |
None | None | N | 0.043 | 0.104 | 0.420570264827 | gnomAD-4.0.0 | 6.57514E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47076E-05 | 0 | 0 |
| M/R | rs1346797877 |
1.189 | 0.065 | N | 0.397 | 0.223 | 0.488477830397 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| M/R | rs1346797877 |
1.189 | 0.065 | N | 0.397 | 0.223 | 0.488477830397 | gnomAD-4.0.0 | 2.05294E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69875E-06 | 0 | 0 |
| M/T | None | None | 0.014 | N | 0.247 | 0.208 | 0.658753162807 | gnomAD-4.0.0 | 5.4745E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29708E-06 | 0 | 1.65695E-05 |
| M/V | rs374376033 |
0.381 | None | N | 0.021 | 0.122 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 1.24018E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs374376033 |
0.381 | None | N | 0.021 | 0.122 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.68927E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs374376033 |
0.381 | None | N | 0.021 | 0.122 | None | gnomAD-4.0.0 | 7.43761E-06 | None | None | None | None | N | None | 1.60248E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1547 | likely_benign | 0.1698 | benign | -1.404 | Destabilizing | 0.002 | N | 0.138 | neutral | None | None | None | None | N |
| M/C | 0.451 | ambiguous | 0.5036 | ambiguous | -1.038 | Destabilizing | 0.497 | N | 0.253 | neutral | None | None | None | None | N |
| M/D | 0.4518 | ambiguous | 0.5075 | ambiguous | -0.423 | Destabilizing | 0.085 | N | 0.472 | neutral | None | None | None | None | N |
| M/E | 0.285 | likely_benign | 0.3106 | benign | -0.424 | Destabilizing | 0.085 | N | 0.396 | neutral | None | None | None | None | N |
| M/F | 0.1667 | likely_benign | 0.1959 | benign | -0.536 | Destabilizing | 0.018 | N | 0.216 | neutral | None | None | None | None | N |
| M/G | 0.406 | ambiguous | 0.4419 | ambiguous | -1.672 | Destabilizing | 0.037 | N | 0.377 | neutral | None | None | None | None | N |
| M/H | 0.2436 | likely_benign | 0.2792 | benign | -0.693 | Destabilizing | 0.497 | N | 0.322 | neutral | None | None | None | None | N |
| M/I | 0.0783 | likely_benign | 0.0911 | benign | -0.738 | Destabilizing | None | N | 0.023 | neutral | N | 0.386821038 | None | None | N |
| M/K | 0.1623 | likely_benign | 0.1771 | benign | -0.414 | Destabilizing | 0.028 | N | 0.343 | neutral | N | 0.391706783 | None | None | N |
| M/L | 0.0872 | likely_benign | 0.0901 | benign | -0.738 | Destabilizing | None | N | 0.043 | neutral | N | 0.418701383 | None | None | N |
| M/N | 0.1946 | likely_benign | 0.219 | benign | -0.248 | Destabilizing | 0.22 | N | 0.418 | neutral | None | None | None | None | N |
| M/P | 0.8613 | likely_pathogenic | 0.875 | pathogenic | -0.933 | Destabilizing | 0.22 | N | 0.438 | neutral | None | None | None | None | N |
| M/Q | 0.1845 | likely_benign | 0.212 | benign | -0.384 | Destabilizing | 0.22 | N | 0.259 | neutral | None | None | None | None | N |
| M/R | 0.1454 | likely_benign | 0.1746 | benign | 0.16 | Stabilizing | 0.065 | N | 0.397 | neutral | N | 0.375006534 | None | None | N |
| M/S | 0.1619 | likely_benign | 0.1759 | benign | -0.793 | Destabilizing | 0.037 | N | 0.324 | neutral | None | None | None | None | N |
| M/T | 0.0905 | likely_benign | 0.0931 | benign | -0.693 | Destabilizing | 0.014 | N | 0.247 | neutral | N | 0.402846497 | None | None | N |
| M/V | 0.0569 | likely_benign | 0.0591 | benign | -0.933 | Destabilizing | None | N | 0.021 | neutral | N | 0.373929099 | None | None | N |
| M/W | 0.4502 | ambiguous | 0.4914 | ambiguous | -0.452 | Destabilizing | 0.788 | D | 0.259 | neutral | None | None | None | None | N |
| M/Y | 0.339 | likely_benign | 0.3791 | ambiguous | -0.463 | Destabilizing | 0.085 | N | 0.372 | 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.