Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25781 | 77566;77567;77568 | chr2:178568791;178568790;178568789 | chr2:179433518;179433517;179433516 |
| N2AB | 24140 | 72643;72644;72645 | chr2:178568791;178568790;178568789 | chr2:179433518;179433517;179433516 |
| N2A | 23213 | 69862;69863;69864 | chr2:178568791;178568790;178568789 | chr2:179433518;179433517;179433516 |
| N2B | 16716 | 50371;50372;50373 | chr2:178568791;178568790;178568789 | chr2:179433518;179433517;179433516 |
| Novex-1 | 16841 | 50746;50747;50748 | chr2:178568791;178568790;178568789 | chr2:179433518;179433517;179433516 |
| Novex-2 | 16908 | 50947;50948;50949 | chr2:178568791;178568790;178568789 | chr2:179433518;179433517;179433516 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 1.0 | N | 0.634 | 0.418 | 0.322786055943 | gnomAD-4.0.0 | 5.47656E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29856E-06 | 0 | 1.6575E-05 |
| D/N | None | None | 1.0 | N | 0.634 | 0.338 | 0.294561560033 | gnomAD-4.0.0 | 2.05371E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52576E-05 | None | 0 | 0 | 8.99794E-07 | 0 | 1.6575E-05 |
| D/V | rs1338611870  |
0.19 | 1.0 | N | 0.692 | 0.568 | 0.630778293416 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| D/V | rs1338611870 |
0.19 | 1.0 | N | 0.692 | 0.568 | 0.630778293416 | gnomAD-4.0.0 | 1.59291E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8608E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.218 | likely_benign | 0.2592 | benign | -0.281 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.49979704 | None | None | N |
| D/C | 0.8158 | likely_pathogenic | 0.856 | pathogenic | -0.07 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/E | 0.1774 | likely_benign | 0.2048 | benign | -0.327 | Destabilizing | 0.999 | D | 0.524 | neutral | N | 0.448829502 | None | None | N |
| D/F | 0.6745 | likely_pathogenic | 0.7275 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/G | 0.4049 | ambiguous | 0.4895 | ambiguous | -0.473 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.470150562 | None | None | N |
| D/H | 0.4866 | ambiguous | 0.5357 | ambiguous | 0.037 | Stabilizing | 1.0 | D | 0.634 | neutral | N | 0.483281295 | None | None | N |
| D/I | 0.4021 | ambiguous | 0.4496 | ambiguous | 0.175 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/K | 0.5472 | ambiguous | 0.5993 | pathogenic | 0.169 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/L | 0.4026 | ambiguous | 0.4516 | ambiguous | 0.175 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| D/M | 0.6431 | likely_pathogenic | 0.6931 | pathogenic | 0.241 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/N | 0.1704 | likely_benign | 0.1906 | benign | -0.07 | Destabilizing | 1.0 | D | 0.634 | neutral | N | 0.473988904 | None | None | N |
| D/P | 0.6019 | likely_pathogenic | 0.6779 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/Q | 0.4645 | ambiguous | 0.5118 | ambiguous | -0.043 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| D/R | 0.6411 | likely_pathogenic | 0.6776 | pathogenic | 0.412 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/S | 0.1962 | likely_benign | 0.2246 | benign | -0.201 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/T | 0.3734 | ambiguous | 0.4269 | ambiguous | -0.056 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/V | 0.2479 | likely_benign | 0.2866 | benign | 0.044 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.470114564 | None | None | N |
| D/W | 0.9461 | likely_pathogenic | 0.959 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| D/Y | 0.3575 | ambiguous | 0.3929 | ambiguous | 0.013 | Stabilizing | 1.0 | D | 0.674 | neutral | N | 0.508982873 | 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.