Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13781 | 41566;41567;41568 | chr2:178636230;178636229;178636228 | chr2:179500957;179500956;179500955 |
| N2AB | 12140 | 36643;36644;36645 | chr2:178636230;178636229;178636228 | chr2:179500957;179500956;179500955 |
| N2A | 11213 | 33862;33863;33864 | chr2:178636230;178636229;178636228 | chr2:179500957;179500956;179500955 |
| N2B | 4716 | 14371;14372;14373 | chr2:178636230;178636229;178636228 | chr2:179500957;179500956;179500955 |
| Novex-1 | 4841 | 14746;14747;14748 | chr2:178636230;178636229;178636228 | chr2:179500957;179500956;179500955 |
| Novex-2 | 4908 | 14947;14948;14949 | chr2:178636230;178636229;178636228 | chr2:179500957;179500956;179500955 |
| 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/C | rs768469221  |
-1.791 | 0.996 | N | 0.705 | 0.325 | 0.406668915854 | gnomAD-2.1.1 | 2.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.77321E-04 | None | 0 | 1.07E-05 | 0 |
| R/C | rs768469221 |
-1.791 | 0.996 | N | 0.705 | 0.325 | 0.406668915854 | gnomAD-4.0.0 | 1.4801E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.18341E-06 | 1.38487E-04 | 0 |
| R/H | rs370878642 |
-2.204 | 0.022 | N | 0.345 | 0.103 | None | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 7.23E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.12E-05 | 0 |
| R/H | rs370878642 |
-2.204 | 0.022 | N | 0.345 | 0.103 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs370878642 |
-2.204 | 0.022 | N | 0.345 | 0.103 | None | gnomAD-4.0.0 | 5.14997E-05 | None | None | None | None | N | None | 1.35744E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.65026E-05 | 3.54669E-05 | 0 |
| R/S | rs768469221 |
-1.785 | 0.228 | N | 0.556 | 0.208 | 0.168933306366 | gnomAD-2.1.1 | 4.86E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.07E-05 | 0 |
| R/S | rs768469221 |
-1.785 | 0.228 | N | 0.556 | 0.208 | 0.168933306366 | 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 |
| R/S | rs768469221 |
-1.785 | 0.228 | N | 0.556 | 0.208 | 0.168933306366 | gnomAD-4.0.0 | 4.45638E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.05065E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7416 | likely_pathogenic | 0.839 | pathogenic | -0.117 | Destabilizing | 0.004 | N | 0.303 | neutral | None | None | None | None | N |
| R/C | 0.2716 | likely_benign | 0.3834 | ambiguous | -0.361 | Destabilizing | 0.996 | D | 0.705 | prob.delet. | N | 0.437364011 | None | None | N |
| R/D | 0.8889 | likely_pathogenic | 0.9291 | pathogenic | -0.083 | Destabilizing | 0.428 | N | 0.631 | neutral | None | None | None | None | N |
| R/E | 0.5752 | likely_pathogenic | 0.7079 | pathogenic | 0.021 | Stabilizing | 0.236 | N | 0.498 | neutral | None | None | None | None | N |
| R/F | 0.8179 | likely_pathogenic | 0.8933 | pathogenic | -0.151 | Destabilizing | 0.842 | D | 0.749 | deleterious | None | None | None | None | N |
| R/G | 0.6246 | likely_pathogenic | 0.7597 | pathogenic | -0.369 | Destabilizing | 0.372 | N | 0.554 | neutral | N | 0.477075378 | None | None | N |
| R/H | 0.142 | likely_benign | 0.1916 | benign | -0.811 | Destabilizing | 0.022 | N | 0.345 | neutral | N | 0.450270933 | None | None | N |
| R/I | 0.5025 | ambiguous | 0.6477 | pathogenic | 0.527 | Stabilizing | 0.842 | D | 0.721 | deleterious | None | None | None | None | N |
| R/K | 0.1712 | likely_benign | 0.2323 | benign | -0.244 | Destabilizing | 0.004 | N | 0.138 | neutral | None | None | None | None | N |
| R/L | 0.5171 | ambiguous | 0.6302 | pathogenic | 0.527 | Stabilizing | 0.589 | D | 0.565 | neutral | N | 0.444156724 | None | None | N |
| R/M | 0.5563 | ambiguous | 0.6981 | pathogenic | -0.051 | Destabilizing | 0.942 | D | 0.606 | neutral | None | None | None | None | N |
| R/N | 0.7876 | likely_pathogenic | 0.8641 | pathogenic | -0.098 | Destabilizing | 0.272 | N | 0.591 | neutral | None | None | None | None | N |
| R/P | 0.9789 | likely_pathogenic | 0.9873 | pathogenic | 0.334 | Stabilizing | 0.911 | D | 0.667 | prob.neutral | N | 0.465328626 | None | None | N |
| R/Q | 0.1528 | likely_benign | 0.2164 | benign | -0.128 | Destabilizing | 0.428 | N | 0.608 | neutral | None | None | None | None | N |
| R/S | 0.7204 | likely_pathogenic | 0.8259 | pathogenic | -0.503 | Destabilizing | 0.228 | N | 0.556 | neutral | N | 0.446938868 | None | None | N |
| R/T | 0.4682 | ambiguous | 0.6313 | pathogenic | -0.238 | Destabilizing | 0.428 | N | 0.621 | neutral | None | None | None | None | N |
| R/V | 0.5807 | likely_pathogenic | 0.7 | pathogenic | 0.334 | Stabilizing | 0.428 | N | 0.705 | prob.delet. | None | None | None | None | N |
| R/W | 0.4122 | ambiguous | 0.5421 | ambiguous | -0.116 | Destabilizing | 0.984 | D | 0.728 | deleterious | None | None | None | None | N |
| R/Y | 0.6336 | likely_pathogenic | 0.7424 | pathogenic | 0.263 | Stabilizing | 0.568 | D | 0.625 | 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.