Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24142 | 72649;72650;72651 | chr2:178573708;178573707;178573706 | chr2:179438435;179438434;179438433 |
| N2AB | 22501 | 67726;67727;67728 | chr2:178573708;178573707;178573706 | chr2:179438435;179438434;179438433 |
| N2A | 21574 | 64945;64946;64947 | chr2:178573708;178573707;178573706 | chr2:179438435;179438434;179438433 |
| N2B | 15077 | 45454;45455;45456 | chr2:178573708;178573707;178573706 | chr2:179438435;179438434;179438433 |
| Novex-1 | 15202 | 45829;45830;45831 | chr2:178573708;178573707;178573706 | chr2:179438435;179438434;179438433 |
| Novex-2 | 15269 | 46030;46031;46032 | chr2:178573708;178573707;178573706 | chr2:179438435;179438434;179438433 |
| 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/I | None | None | 0.884 | D | 0.325 | 0.237 | 0.218112801441 | gnomAD-4.0.0 | 7.18185E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.26877E-07 | 0 | 0 |
| L/P | rs986884075  |
-1.796 | 1.0 | D | 0.917 | 0.732 | 0.905059791241 | gnomAD-2.1.1 | 5.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.09E-05 | 0 |
| L/P | rs986884075 |
-1.796 | 1.0 | D | 0.917 | 0.732 | 0.905059791241 | gnomAD-4.0.0 | 1.36733E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.76305E-05 | 0 | 0 |
| L/Q | rs986884075 |
None | 1.0 | D | 0.909 | 0.615 | 0.873585393695 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/Q | rs986884075 |
None | 1.0 | D | 0.909 | 0.615 | 0.873585393695 | gnomAD-4.0.0 | 1.94594E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.61856E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9196 | likely_pathogenic | 0.9304 | pathogenic | -2.532 | Highly Destabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | N |
| L/C | 0.8414 | likely_pathogenic | 0.864 | pathogenic | -1.703 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -3.246 | Highly Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| L/E | 0.9977 | likely_pathogenic | 0.9977 | pathogenic | -2.911 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| L/F | 0.5819 | likely_pathogenic | 0.6196 | pathogenic | -1.506 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| L/G | 0.9907 | likely_pathogenic | 0.9915 | pathogenic | -3.164 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| L/H | 0.9933 | likely_pathogenic | 0.9937 | pathogenic | -2.97 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| L/I | 0.1063 | likely_benign | 0.1148 | benign | -0.635 | Destabilizing | 0.884 | D | 0.325 | neutral | D | 0.530936385 | None | None | N |
| L/K | 0.9965 | likely_pathogenic | 0.9965 | pathogenic | -1.912 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| L/M | 0.3151 | likely_benign | 0.3493 | ambiguous | -0.781 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| L/N | 0.9976 | likely_pathogenic | 0.9977 | pathogenic | -2.647 | Highly Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| L/P | 0.9961 | likely_pathogenic | 0.9956 | pathogenic | -1.257 | Destabilizing | 1.0 | D | 0.917 | deleterious | D | 0.568238341 | None | None | N |
| L/Q | 0.9907 | likely_pathogenic | 0.9913 | pathogenic | -2.257 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | D | 0.568238341 | None | None | N |
| L/R | 0.9916 | likely_pathogenic | 0.9914 | pathogenic | -2.062 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.568238341 | None | None | N |
| L/S | 0.9914 | likely_pathogenic | 0.9923 | pathogenic | -3.213 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/T | 0.9593 | likely_pathogenic | 0.9641 | pathogenic | -2.703 | Highly Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| L/V | 0.1344 | likely_benign | 0.1565 | benign | -1.257 | Destabilizing | 0.981 | D | 0.607 | neutral | N | 0.508768814 | None | None | N |
| L/W | 0.9799 | likely_pathogenic | 0.9807 | pathogenic | -1.958 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/Y | 0.9744 | likely_pathogenic | 0.978 | pathogenic | -1.682 | Destabilizing | 1.0 | D | 0.796 | 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.