Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30351 | 91276;91277;91278 | chr2:178551849;178551848;178551847 | chr2:179416576;179416575;179416574 |
| N2AB | 28710 | 86353;86354;86355 | chr2:178551849;178551848;178551847 | chr2:179416576;179416575;179416574 |
| N2A | 27783 | 83572;83573;83574 | chr2:178551849;178551848;178551847 | chr2:179416576;179416575;179416574 |
| N2B | 21286 | 64081;64082;64083 | chr2:178551849;178551848;178551847 | chr2:179416576;179416575;179416574 |
| Novex-1 | 21411 | 64456;64457;64458 | chr2:178551849;178551848;178551847 | chr2:179416576;179416575;179416574 |
| Novex-2 | 21478 | 64657;64658;64659 | chr2:178551849;178551848;178551847 | chr2:179416576;179416575;179416574 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs1357760095  |
-0.965 | 0.985 | N | 0.755 | 0.453 | 0.301455362545 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs1357760095 |
-0.965 | 0.985 | N | 0.755 | 0.453 | 0.301455362545 | gnomAD-4.0.0 | 1.59108E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77285E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | None | None | 0.973 | N | 0.749 | 0.593 | 0.664550491324 | gnomAD-4.0.0 | 1.59109E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85794E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7095 | likely_pathogenic | 0.8051 | pathogenic | -0.698 | Destabilizing | 0.946 | D | 0.68 | prob.neutral | N | 0.489272457 | None | None | I |
| D/C | 0.923 | likely_pathogenic | 0.9475 | pathogenic | -0.199 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/E | 0.7261 | likely_pathogenic | 0.7976 | pathogenic | -0.678 | Destabilizing | 0.834 | D | 0.43 | neutral | N | 0.491385597 | None | None | I |
| D/F | 0.9513 | likely_pathogenic | 0.9716 | pathogenic | -0.574 | Destabilizing | 0.998 | D | 0.749 | deleterious | None | None | None | None | I |
| D/G | 0.6094 | likely_pathogenic | 0.7001 | pathogenic | -1.009 | Destabilizing | 0.716 | D | 0.6 | neutral | N | 0.507910144 | None | None | I |
| D/H | 0.7781 | likely_pathogenic | 0.8453 | pathogenic | -0.928 | Destabilizing | 0.985 | D | 0.755 | deleterious | N | 0.502376735 | None | None | I |
| D/I | 0.9068 | likely_pathogenic | 0.9458 | pathogenic | 0.114 | Stabilizing | 0.979 | D | 0.753 | deleterious | None | None | None | None | I |
| D/K | 0.9056 | likely_pathogenic | 0.9403 | pathogenic | -0.29 | Destabilizing | 0.921 | D | 0.671 | neutral | None | None | None | None | I |
| D/L | 0.8813 | likely_pathogenic | 0.9244 | pathogenic | 0.114 | Stabilizing | 0.959 | D | 0.746 | deleterious | None | None | None | None | I |
| D/M | 0.955 | likely_pathogenic | 0.9722 | pathogenic | 0.635 | Stabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | I |
| D/N | 0.1413 | likely_benign | 0.1627 | benign | -0.659 | Destabilizing | 0.035 | N | 0.253 | neutral | N | 0.520617817 | None | None | I |
| D/P | 0.9513 | likely_pathogenic | 0.9689 | pathogenic | -0.133 | Destabilizing | 0.979 | D | 0.784 | deleterious | None | None | None | None | I |
| D/Q | 0.8811 | likely_pathogenic | 0.9185 | pathogenic | -0.559 | Destabilizing | 0.959 | D | 0.766 | deleterious | None | None | None | None | I |
| D/R | 0.8916 | likely_pathogenic | 0.9306 | pathogenic | -0.26 | Destabilizing | 0.959 | D | 0.769 | deleterious | None | None | None | None | I |
| D/S | 0.2927 | likely_benign | 0.375 | ambiguous | -0.895 | Destabilizing | 0.769 | D | 0.571 | neutral | None | None | None | None | I |
| D/T | 0.5001 | ambiguous | 0.5971 | pathogenic | -0.635 | Destabilizing | 0.921 | D | 0.668 | neutral | None | None | None | None | I |
| D/V | 0.7997 | likely_pathogenic | 0.8702 | pathogenic | -0.133 | Destabilizing | 0.973 | D | 0.749 | deleterious | N | 0.509605211 | None | None | I |
| D/W | 0.9889 | likely_pathogenic | 0.9932 | pathogenic | -0.424 | Destabilizing | 0.998 | D | 0.736 | prob.delet. | None | None | None | None | I |
| D/Y | 0.748 | likely_pathogenic | 0.8313 | pathogenic | -0.336 | Destabilizing | 0.998 | D | 0.745 | deleterious | D | 0.537370704 | None | None | I |
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.