Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20498 | 61717;61718;61719 | chr2:178590233;178590232;178590231 | chr2:179454960;179454959;179454958 |
| N2AB | 18857 | 56794;56795;56796 | chr2:178590233;178590232;178590231 | chr2:179454960;179454959;179454958 |
| N2A | 17930 | 54013;54014;54015 | chr2:178590233;178590232;178590231 | chr2:179454960;179454959;179454958 |
| N2B | 11433 | 34522;34523;34524 | chr2:178590233;178590232;178590231 | chr2:179454960;179454959;179454958 |
| Novex-1 | 11558 | 34897;34898;34899 | chr2:178590233;178590232;178590231 | chr2:179454960;179454959;179454958 |
| Novex-2 | 11625 | 35098;35099;35100 | chr2:178590233;178590232;178590231 | chr2:179454960;179454959;179454958 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs145131899  |
0.567 | 0.946 | N | 0.719 | 0.224 | None | gnomAD-2.1.1 | 1.74E-05 | None | None | None | None | N | None | 0 | 9.26E-05 | None | 0 | 0 | None | 0 | None | 0 | 9.47E-06 | 0 |
| A/V | rs145131899 |
0.567 | 0.946 | N | 0.719 | 0.224 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs145131899 |
0.567 | 0.946 | N | 0.719 | 0.224 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/V | rs145131899 |
0.567 | 0.946 | N | 0.719 | 0.224 | None | gnomAD-4.0.0 | 3.94527E-06 | None | None | None | None | N | None | 0 | 3.5025E-05 | None | 0 | 0 | None | 0 | 0 | 2.45102E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6929 | likely_pathogenic | 0.6943 | pathogenic | -0.761 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | N |
| A/D | 0.9962 | likely_pathogenic | 0.9963 | pathogenic | -1.516 | Destabilizing | 0.984 | D | 0.833 | deleterious | N | 0.479027063 | None | None | N |
| A/E | 0.9943 | likely_pathogenic | 0.9942 | pathogenic | -1.46 | Destabilizing | 0.988 | D | 0.817 | deleterious | None | None | None | None | N |
| A/F | 0.9615 | likely_pathogenic | 0.9639 | pathogenic | -0.772 | Destabilizing | 0.996 | D | 0.867 | deleterious | None | None | None | None | N |
| A/G | 0.1532 | likely_benign | 0.1951 | benign | -1.251 | Destabilizing | 0.004 | N | 0.451 | neutral | N | 0.459384852 | None | None | N |
| A/H | 0.9955 | likely_pathogenic | 0.9948 | pathogenic | -1.546 | Destabilizing | 0.999 | D | 0.866 | deleterious | None | None | None | None | N |
| A/I | 0.9029 | likely_pathogenic | 0.9058 | pathogenic | -0.065 | Destabilizing | 0.996 | D | 0.804 | deleterious | None | None | None | None | N |
| A/K | 0.9981 | likely_pathogenic | 0.9978 | pathogenic | -1.264 | Destabilizing | 0.988 | D | 0.81 | deleterious | None | None | None | None | N |
| A/L | 0.7736 | likely_pathogenic | 0.7759 | pathogenic | -0.065 | Destabilizing | 0.959 | D | 0.816 | deleterious | None | None | None | None | N |
| A/M | 0.8837 | likely_pathogenic | 0.8792 | pathogenic | -0.059 | Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | N |
| A/N | 0.9878 | likely_pathogenic | 0.9867 | pathogenic | -1.11 | Destabilizing | 0.976 | D | 0.834 | deleterious | None | None | None | None | N |
| A/P | 0.9864 | likely_pathogenic | 0.9883 | pathogenic | -0.301 | Destabilizing | 0.995 | D | 0.801 | deleterious | N | 0.479027063 | None | None | N |
| A/Q | 0.9869 | likely_pathogenic | 0.9847 | pathogenic | -1.145 | Destabilizing | 0.996 | D | 0.784 | deleterious | None | None | None | None | N |
| A/R | 0.9945 | likely_pathogenic | 0.9934 | pathogenic | -1.043 | Destabilizing | 0.988 | D | 0.805 | deleterious | None | None | None | None | N |
| A/S | 0.3474 | ambiguous | 0.3431 | ambiguous | -1.474 | Destabilizing | 0.896 | D | 0.671 | neutral | N | 0.467163778 | None | None | N |
| A/T | 0.5545 | ambiguous | 0.5243 | ambiguous | -1.314 | Destabilizing | 0.946 | D | 0.728 | prob.delet. | N | 0.483280432 | None | None | N |
| A/V | 0.6305 | likely_pathogenic | 0.6317 | pathogenic | -0.301 | Destabilizing | 0.946 | D | 0.719 | prob.delet. | N | 0.431944748 | None | None | N |
| A/W | 0.9974 | likely_pathogenic | 0.9974 | pathogenic | -1.312 | Destabilizing | 0.999 | D | 0.887 | deleterious | None | None | None | None | N |
| A/Y | 0.9882 | likely_pathogenic | 0.9879 | pathogenic | -0.823 | Destabilizing | 0.996 | D | 0.874 | deleterious | 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.