Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32070 | 96433;96434;96435 | chr2:178543936;178543935;178543934 | chr2:179408663;179408662;179408661 |
| N2AB | 30429 | 91510;91511;91512 | chr2:178543936;178543935;178543934 | chr2:179408663;179408662;179408661 |
| N2A | 29502 | 88729;88730;88731 | chr2:178543936;178543935;178543934 | chr2:179408663;179408662;179408661 |
| N2B | 23005 | 69238;69239;69240 | chr2:178543936;178543935;178543934 | chr2:179408663;179408662;179408661 |
| Novex-1 | 23130 | 69613;69614;69615 | chr2:178543936;178543935;178543934 | chr2:179408663;179408662;179408661 |
| Novex-2 | 23197 | 69814;69815;69816 | chr2:178543936;178543935;178543934 | chr2:179408663;179408662;179408661 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/Q | rs748827491  |
-2.419 | 1.0 | D | 0.897 | 0.794 | 0.895610212195 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| L/Q | rs748827491 |
-2.419 | 1.0 | D | 0.897 | 0.794 | 0.895610212195 | gnomAD-4.0.0 | 1.36847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79904E-06 | 0 | 0 |
| L/R | None | None | 1.0 | D | 0.895 | 0.815 | 0.891007205168 | gnomAD-4.0.0 | 6.84236E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99522E-07 | 0 | 0 |
| L/V | None | None | 0.999 | N | 0.672 | 0.53 | 0.711190949314 | gnomAD-4.0.0 | 7.95715E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.38635E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9482 | likely_pathogenic | 0.9445 | pathogenic | -2.561 | Highly Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/C | 0.8682 | likely_pathogenic | 0.8674 | pathogenic | -1.599 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| L/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.326 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| L/E | 0.9986 | likely_pathogenic | 0.9983 | pathogenic | -3.003 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| L/F | 0.6783 | likely_pathogenic | 0.6046 | pathogenic | -1.6 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/G | 0.9939 | likely_pathogenic | 0.9934 | pathogenic | -3.142 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| L/H | 0.993 | likely_pathogenic | 0.9912 | pathogenic | -2.974 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/I | 0.3114 | likely_benign | 0.2655 | benign | -0.795 | Destabilizing | 0.999 | D | 0.665 | neutral | N | 0.505871996 | None | None | N |
| L/K | 0.9968 | likely_pathogenic | 0.9962 | pathogenic | -2.037 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| L/M | 0.3255 | likely_benign | 0.3123 | benign | -0.933 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| L/N | 0.9984 | likely_pathogenic | 0.9981 | pathogenic | -2.842 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| L/P | 0.9984 | likely_pathogenic | 0.9981 | pathogenic | -1.378 | Destabilizing | 1.0 | D | 0.896 | deleterious | D | 0.585939246 | None | None | N |
| L/Q | 0.9889 | likely_pathogenic | 0.9873 | pathogenic | -2.418 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.585939246 | None | None | N |
| L/R | 0.9923 | likely_pathogenic | 0.9911 | pathogenic | -2.268 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.585939246 | None | None | N |
| L/S | 0.996 | likely_pathogenic | 0.9951 | pathogenic | -3.265 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/T | 0.9867 | likely_pathogenic | 0.9841 | pathogenic | -2.776 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/V | 0.3011 | likely_benign | 0.2729 | benign | -1.378 | Destabilizing | 0.999 | D | 0.672 | neutral | N | 0.516849908 | None | None | N |
| L/W | 0.9793 | likely_pathogenic | 0.9689 | pathogenic | -1.942 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/Y | 0.9758 | likely_pathogenic | 0.9676 | pathogenic | -1.776 | Destabilizing | 1.0 | D | 0.85 | 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.