Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25848 | 77767;77768;77769 | chr2:178568590;178568589;178568588 | chr2:179433317;179433316;179433315 |
| N2AB | 24207 | 72844;72845;72846 | chr2:178568590;178568589;178568588 | chr2:179433317;179433316;179433315 |
| N2A | 23280 | 70063;70064;70065 | chr2:178568590;178568589;178568588 | chr2:179433317;179433316;179433315 |
| N2B | 16783 | 50572;50573;50574 | chr2:178568590;178568589;178568588 | chr2:179433317;179433316;179433315 |
| Novex-1 | 16908 | 50947;50948;50949 | chr2:178568590;178568589;178568588 | chr2:179433317;179433316;179433315 |
| Novex-2 | 16975 | 51148;51149;51150 | chr2:178568590;178568589;178568588 | chr2:179433317;179433316;179433315 |
| 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/A | rs773448900  |
-0.296 | 0.025 | N | 0.52 | 0.289 | 0.301455362545 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs763227305 |
0.043 | 0.997 | N | 0.712 | 0.324 | 0.337378238328 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.58E-05 | 0 |
| D/N | rs763227305 |
0.043 | 0.997 | N | 0.712 | 0.324 | 0.337378238328 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 1.93573E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs763227305 |
0.043 | 0.997 | N | 0.712 | 0.324 | 0.337378238328 | gnomAD-4.0.0 | 2.35551E-05 | None | None | None | None | N | None | 1.33636E-05 | 3.336E-05 | None | 0 | 2.22995E-05 | None | 0 | 0 | 2.79764E-05 | 1.0982E-05 | 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 | 0.1534 | likely_benign | 0.1443 | benign | -0.421 | Destabilizing | 0.025 | N | 0.52 | neutral | N | 0.494557084 | None | None | N |
| D/C | 0.5279 | ambiguous | 0.4953 | ambiguous | 0.153 | Stabilizing | 0.997 | D | 0.786 | deleterious | None | None | None | None | N |
| D/E | 0.1641 | likely_benign | 0.1581 | benign | -0.343 | Destabilizing | 0.099 | N | 0.325 | neutral | N | 0.457289562 | None | None | N |
| D/F | 0.6273 | likely_pathogenic | 0.5598 | ambiguous | -0.44 | Destabilizing | 0.997 | D | 0.798 | deleterious | None | None | None | None | N |
| D/G | 0.1841 | likely_benign | 0.1726 | benign | -0.634 | Destabilizing | 0.805 | D | 0.676 | prob.neutral | N | 0.457772352 | None | None | N |
| D/H | 0.2577 | likely_benign | 0.2311 | benign | -0.522 | Destabilizing | 0.999 | D | 0.76 | deleterious | N | 0.510662687 | None | None | N |
| D/I | 0.3776 | ambiguous | 0.3275 | benign | 0.1 | Stabilizing | 0.975 | D | 0.802 | deleterious | None | None | None | None | N |
| D/K | 0.3818 | ambiguous | 0.3655 | ambiguous | 0.326 | Stabilizing | 0.975 | D | 0.741 | deleterious | None | None | None | None | N |
| D/L | 0.4211 | ambiguous | 0.3882 | ambiguous | 0.1 | Stabilizing | 0.95 | D | 0.782 | deleterious | None | None | None | None | N |
| D/M | 0.6153 | likely_pathogenic | 0.575 | pathogenic | 0.44 | Stabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | N |
| D/N | 0.0829 | likely_benign | 0.0806 | benign | 0.017 | Stabilizing | 0.997 | D | 0.712 | prob.delet. | N | 0.420291399 | None | None | N |
| D/P | 0.6461 | likely_pathogenic | 0.6424 | pathogenic | -0.052 | Destabilizing | 0.987 | D | 0.779 | deleterious | None | None | None | None | N |
| D/Q | 0.3151 | likely_benign | 0.2975 | benign | 0.051 | Stabilizing | 0.975 | D | 0.755 | deleterious | None | None | None | None | N |
| D/R | 0.4316 | ambiguous | 0.4094 | ambiguous | 0.345 | Stabilizing | 0.975 | D | 0.795 | deleterious | None | None | None | None | N |
| D/S | 0.0976 | likely_benign | 0.0914 | benign | -0.095 | Destabilizing | 0.845 | D | 0.643 | neutral | None | None | None | None | N |
| D/T | 0.1704 | likely_benign | 0.1633 | benign | 0.076 | Stabilizing | 0.975 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/V | 0.2214 | likely_benign | 0.1977 | benign | -0.052 | Destabilizing | 0.935 | D | 0.764 | deleterious | N | 0.495287803 | None | None | N |
| D/W | 0.9009 | likely_pathogenic | 0.8871 | pathogenic | -0.309 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2668 | likely_benign | 0.231 | benign | -0.2 | Destabilizing | 0.999 | D | 0.797 | deleterious | N | 0.521647685 | 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.