Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22653 | 68182;68183;68184 | chr2:178579073;178579072;178579071 | chr2:179443800;179443799;179443798 |
| N2AB | 21012 | 63259;63260;63261 | chr2:178579073;178579072;178579071 | chr2:179443800;179443799;179443798 |
| N2A | 20085 | 60478;60479;60480 | chr2:178579073;178579072;178579071 | chr2:179443800;179443799;179443798 |
| N2B | 13588 | 40987;40988;40989 | chr2:178579073;178579072;178579071 | chr2:179443800;179443799;179443798 |
| Novex-1 | 13713 | 41362;41363;41364 | chr2:178579073;178579072;178579071 | chr2:179443800;179443799;179443798 |
| Novex-2 | 13780 | 41563;41564;41565 | chr2:178579073;178579072;178579071 | chr2:179443800;179443799;179443798 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs749873981  |
None | 1.0 | N | 0.853 | 0.564 | 0.610807630001 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/C | rs749873981 |
None | 1.0 | N | 0.853 | 0.564 | 0.610807630001 | gnomAD-4.0.0 | 6.5799E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47145E-05 | 0 | 0 |
| F/L | rs72646877 |
-1.236 | 0.999 | N | 0.587 | 0.521 | 0.432266382184 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| F/L | rs72646877 |
-1.236 | 0.999 | N | 0.587 | 0.521 | 0.432266382184 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| F/L | rs72646877 |
-1.236 | 0.999 | N | 0.587 | 0.521 | 0.432266382184 | gnomAD-4.0.0 | 9.29831E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18689E-05 | 0 | 1.60169E-05 |
| F/Y | rs749873981 |
-0.607 | 0.999 | N | 0.607 | 0.37 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| F/Y | rs749873981 |
-0.607 | 0.999 | N | 0.607 | 0.37 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/Y | rs749873981 |
-0.607 | 0.999 | N | 0.607 | 0.37 | None | gnomAD-4.0.0 | 1.4878E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.03473E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.739 | likely_pathogenic | 0.6753 | pathogenic | -2.652 | Highly Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| F/C | 0.4986 | ambiguous | 0.4285 | ambiguous | -1.89 | Destabilizing | 1.0 | D | 0.853 | deleterious | N | 0.519599096 | None | None | N |
| F/D | 0.9718 | likely_pathogenic | 0.9576 | pathogenic | -2.207 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| F/E | 0.9653 | likely_pathogenic | 0.9483 | pathogenic | -2.029 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| F/G | 0.9355 | likely_pathogenic | 0.911 | pathogenic | -3.076 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| F/H | 0.892 | likely_pathogenic | 0.8534 | pathogenic | -1.383 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| F/I | 0.2315 | likely_benign | 0.2057 | benign | -1.304 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.454238109 | None | None | N |
| F/K | 0.964 | likely_pathogenic | 0.9448 | pathogenic | -2.114 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| F/L | 0.8883 | likely_pathogenic | 0.8674 | pathogenic | -1.304 | Destabilizing | 0.999 | D | 0.587 | neutral | N | 0.467340692 | None | None | N |
| F/M | 0.5197 | ambiguous | 0.4895 | ambiguous | -1.057 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| F/N | 0.9125 | likely_pathogenic | 0.8775 | pathogenic | -2.449 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| F/P | 0.9703 | likely_pathogenic | 0.9593 | pathogenic | -1.758 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| F/Q | 0.9458 | likely_pathogenic | 0.9209 | pathogenic | -2.395 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| F/R | 0.9393 | likely_pathogenic | 0.9113 | pathogenic | -1.563 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| F/S | 0.8023 | likely_pathogenic | 0.7329 | pathogenic | -3.22 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | N | 0.471688407 | None | None | N |
| F/T | 0.6994 | likely_pathogenic | 0.6351 | pathogenic | -2.927 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| F/V | 0.2885 | likely_benign | 0.2581 | benign | -1.758 | Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.437110999 | None | None | N |
| F/W | 0.591 | likely_pathogenic | 0.5533 | ambiguous | -0.355 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| F/Y | 0.302 | likely_benign | 0.2576 | benign | -0.732 | Destabilizing | 0.999 | D | 0.607 | neutral | N | 0.502802847 | 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.