Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26901 | 80926;80927;80928 | chr2:178565431;178565430;178565429 | chr2:179430158;179430157;179430156 |
| N2AB | 25260 | 76003;76004;76005 | chr2:178565431;178565430;178565429 | chr2:179430158;179430157;179430156 |
| N2A | 24333 | 73222;73223;73224 | chr2:178565431;178565430;178565429 | chr2:179430158;179430157;179430156 |
| N2B | 17836 | 53731;53732;53733 | chr2:178565431;178565430;178565429 | chr2:179430158;179430157;179430156 |
| Novex-1 | 17961 | 54106;54107;54108 | chr2:178565431;178565430;178565429 | chr2:179430158;179430157;179430156 |
| Novex-2 | 18028 | 54307;54308;54309 | chr2:178565431;178565430;178565429 | chr2:179430158;179430157;179430156 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.58 | N | 0.513 | 0.163 | 0.384752662912 | gnomAD-4.0.0 | 6.84347E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15977E-05 | 0 |
| I/V | rs201562505  |
-1.139 | 0.02 | N | 0.304 | 0.106 | None | gnomAD-2.1.1 | 1.49395E-03 | None | None | None | None | N | None | 8.27E-05 | 3.96915E-04 | None | 3.15159E-02 | 0 | None | 6.54E-05 | None | 0 | 4.61226E-04 | 2.11268E-03 |
| I/V | rs201562505 |
-1.139 | 0.02 | N | 0.304 | 0.106 | None | gnomAD-3.1.2 | 9.92898E-04 | None | None | None | None | N | None | 2.41E-05 | 1.90164E-03 | 0 | 2.68012E-02 | 0 | None | 0 | 3.16456E-03 | 2.94118E-04 | 2.07039E-04 | 2.87356E-03 |
| I/V | rs201562505 |
-1.139 | 0.02 | N | 0.304 | 0.106 | None | gnomAD-4.0.0 | 9.26589E-04 | None | None | None | None | N | None | 1.06687E-04 | 8.17157E-04 | None | 3.29863E-02 | 0 | None | 0 | 5.28751E-03 | 2.1532E-04 | 9.88468E-05 | 2.67431E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8376 | likely_pathogenic | 0.8064 | pathogenic | -2.865 | Highly Destabilizing | 0.91 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/C | 0.87 | likely_pathogenic | 0.8469 | pathogenic | -2.231 | Highly Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| I/D | 0.995 | likely_pathogenic | 0.9936 | pathogenic | -3.466 | Highly Destabilizing | 0.998 | D | 0.847 | deleterious | None | None | None | None | N |
| I/E | 0.9907 | likely_pathogenic | 0.9895 | pathogenic | -3.193 | Highly Destabilizing | 0.993 | D | 0.849 | deleterious | None | None | None | None | N |
| I/F | 0.3496 | ambiguous | 0.3427 | ambiguous | -1.734 | Destabilizing | 0.991 | D | 0.747 | deleterious | N | 0.479151967 | None | None | N |
| I/G | 0.9646 | likely_pathogenic | 0.9591 | pathogenic | -3.462 | Highly Destabilizing | 0.993 | D | 0.851 | deleterious | None | None | None | None | N |
| I/H | 0.9752 | likely_pathogenic | 0.9701 | pathogenic | -2.956 | Highly Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| I/K | 0.9776 | likely_pathogenic | 0.9756 | pathogenic | -2.483 | Highly Destabilizing | 0.993 | D | 0.849 | deleterious | None | None | None | None | N |
| I/L | 0.1814 | likely_benign | 0.1665 | benign | -1.109 | Destabilizing | 0.58 | D | 0.513 | neutral | N | 0.465905393 | None | None | N |
| I/M | 0.1929 | likely_benign | 0.1803 | benign | -1.076 | Destabilizing | 0.991 | D | 0.713 | prob.delet. | N | 0.472822091 | None | None | N |
| I/N | 0.9161 | likely_pathogenic | 0.9009 | pathogenic | -2.987 | Highly Destabilizing | 0.997 | D | 0.843 | deleterious | N | 0.491179835 | None | None | N |
| I/P | 0.992 | likely_pathogenic | 0.9884 | pathogenic | -1.679 | Destabilizing | 0.998 | D | 0.834 | deleterious | None | None | None | None | N |
| I/Q | 0.9771 | likely_pathogenic | 0.9742 | pathogenic | -2.771 | Highly Destabilizing | 0.998 | D | 0.849 | deleterious | None | None | None | None | N |
| I/R | 0.9704 | likely_pathogenic | 0.9669 | pathogenic | -2.212 | Highly Destabilizing | 0.993 | D | 0.851 | deleterious | None | None | None | None | N |
| I/S | 0.8884 | likely_pathogenic | 0.8609 | pathogenic | -3.662 | Highly Destabilizing | 0.991 | D | 0.819 | deleterious | N | 0.467795661 | None | None | N |
| I/T | 0.876 | likely_pathogenic | 0.8429 | pathogenic | -3.231 | Highly Destabilizing | 0.939 | D | 0.765 | deleterious | N | 0.472061622 | None | None | N |
| I/V | 0.1122 | likely_benign | 0.1017 | benign | -1.679 | Destabilizing | 0.02 | N | 0.304 | neutral | N | 0.410606683 | None | None | N |
| I/W | 0.9673 | likely_pathogenic | 0.9609 | pathogenic | -2.186 | Highly Destabilizing | 0.999 | D | 0.818 | deleterious | None | None | None | None | N |
| I/Y | 0.8575 | likely_pathogenic | 0.8482 | pathogenic | -1.912 | Destabilizing | 0.998 | D | 0.759 | 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.