Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25901 | 77926;77927;77928 | chr2:178568431;178568430;178568429 | chr2:179433158;179433157;179433156 |
| N2AB | 24260 | 73003;73004;73005 | chr2:178568431;178568430;178568429 | chr2:179433158;179433157;179433156 |
| N2A | 23333 | 70222;70223;70224 | chr2:178568431;178568430;178568429 | chr2:179433158;179433157;179433156 |
| N2B | 16836 | 50731;50732;50733 | chr2:178568431;178568430;178568429 | chr2:179433158;179433157;179433156 |
| Novex-1 | 16961 | 51106;51107;51108 | chr2:178568431;178568430;178568429 | chr2:179433158;179433157;179433156 |
| Novex-2 | 17028 | 51307;51308;51309 | chr2:178568431;178568430;178568429 | chr2:179433158;179433157;179433156 |
| 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/E | rs765603724  |
0.044 | 0.767 | N | 0.248 | 0.141 | 0.323886383625 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| D/E | rs765603724 |
0.044 | 0.767 | N | 0.248 | 0.141 | 0.323886383625 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs765603724 |
0.044 | 0.767 | N | 0.248 | 0.141 | 0.323886383625 | gnomAD-4.0.0 | 3.04506E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61493E-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 | 0.168 | likely_benign | 0.1908 | benign | -0.473 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | N | 0.521404464 | None | None | N |
| D/C | 0.5058 | ambiguous | 0.5373 | ambiguous | 0.035 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/E | 0.1272 | likely_benign | 0.1372 | benign | -0.378 | Destabilizing | 0.767 | D | 0.248 | neutral | N | 0.464068314 | None | None | N |
| D/F | 0.545 | ambiguous | 0.6056 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/G | 0.2005 | likely_benign | 0.2424 | benign | -0.701 | Destabilizing | 0.998 | D | 0.73 | prob.delet. | D | 0.522097897 | None | None | N |
| D/H | 0.2559 | likely_benign | 0.303 | benign | -0.472 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.483307748 | None | None | N |
| D/I | 0.2869 | likely_benign | 0.3175 | benign | 0.089 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| D/K | 0.35 | ambiguous | 0.4055 | ambiguous | 0.158 | Stabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/L | 0.3239 | likely_benign | 0.3515 | ambiguous | 0.089 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/M | 0.4961 | ambiguous | 0.5179 | ambiguous | 0.416 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| D/N | 0.0971 | likely_benign | 0.1163 | benign | -0.156 | Destabilizing | 0.999 | D | 0.641 | neutral | N | 0.510976826 | None | None | N |
| D/P | 0.9133 | likely_pathogenic | 0.9266 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/Q | 0.2845 | likely_benign | 0.3244 | benign | -0.112 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/R | 0.404 | ambiguous | 0.4659 | ambiguous | 0.257 | Stabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | N |
| D/S | 0.0985 | likely_benign | 0.1158 | benign | -0.291 | Destabilizing | 0.997 | D | 0.645 | neutral | None | None | None | None | N |
| D/T | 0.163 | likely_benign | 0.1798 | benign | -0.111 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| D/V | 0.1867 | likely_benign | 0.1997 | benign | -0.076 | Destabilizing | 0.999 | D | 0.78 | deleterious | N | 0.488369325 | None | None | N |
| D/W | 0.8583 | likely_pathogenic | 0.8771 | pathogenic | -0.27 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/Y | 0.247 | likely_benign | 0.2858 | benign | -0.185 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.475825783 | 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.