Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24736 | 74431;74432;74433 | chr2:178571926;178571925;178571924 | chr2:179436653;179436652;179436651 |
| N2AB | 23095 | 69508;69509;69510 | chr2:178571926;178571925;178571924 | chr2:179436653;179436652;179436651 |
| N2A | 22168 | 66727;66728;66729 | chr2:178571926;178571925;178571924 | chr2:179436653;179436652;179436651 |
| N2B | 15671 | 47236;47237;47238 | chr2:178571926;178571925;178571924 | chr2:179436653;179436652;179436651 |
| Novex-1 | 15796 | 47611;47612;47613 | chr2:178571926;178571925;178571924 | chr2:179436653;179436652;179436651 |
| Novex-2 | 15863 | 47812;47813;47814 | chr2:178571926;178571925;178571924 | chr2:179436653;179436652;179436651 |
| 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/G | rs762510108  |
0.276 | 0.892 | N | 0.545 | 0.502 | 0.381916209588 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| D/G | rs762510108 |
0.276 | 0.892 | N | 0.545 | 0.502 | 0.381916209588 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/G | rs762510108 |
0.276 | 0.892 | N | 0.545 | 0.502 | 0.381916209588 | gnomAD-4.0.0 | 2.47967E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39111E-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 | 0.1855 | likely_benign | 0.2079 | benign | -0.451 | Destabilizing | 0.892 | D | 0.578 | neutral | N | 0.519474171 | None | None | N |
| D/C | 0.6746 | likely_pathogenic | 0.7099 | pathogenic | -0.139 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/E | 0.1532 | likely_benign | 0.169 | benign | -0.573 | Destabilizing | 0.025 | N | 0.334 | neutral | N | 0.410805124 | None | None | N |
| D/F | 0.6505 | likely_pathogenic | 0.6786 | pathogenic | 0.019 | Stabilizing | 0.987 | D | 0.76 | deleterious | None | None | None | None | N |
| D/G | 0.3161 | likely_benign | 0.3514 | ambiguous | -0.787 | Destabilizing | 0.892 | D | 0.545 | neutral | N | 0.490505403 | None | None | N |
| D/H | 0.3054 | likely_benign | 0.3452 | ambiguous | -0.138 | Destabilizing | 0.12 | N | 0.415 | neutral | N | 0.508027814 | None | None | N |
| D/I | 0.3456 | ambiguous | 0.3884 | ambiguous | 0.429 | Stabilizing | 0.987 | D | 0.763 | deleterious | None | None | None | None | N |
| D/K | 0.4587 | ambiguous | 0.5226 | ambiguous | -0.083 | Destabilizing | 0.95 | D | 0.644 | neutral | None | None | None | None | N |
| D/L | 0.4277 | ambiguous | 0.47 | ambiguous | 0.429 | Stabilizing | 0.975 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/M | 0.5999 | likely_pathogenic | 0.6401 | pathogenic | 0.757 | Stabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| D/N | 0.1126 | likely_benign | 0.1236 | benign | -0.667 | Destabilizing | 0.892 | D | 0.517 | neutral | N | 0.503427284 | None | None | N |
| D/P | 0.749 | likely_pathogenic | 0.7873 | pathogenic | 0.161 | Stabilizing | 0.987 | D | 0.712 | prob.delet. | None | None | None | None | N |
| D/Q | 0.3664 | ambiguous | 0.4086 | ambiguous | -0.518 | Destabilizing | 0.95 | D | 0.629 | neutral | None | None | None | None | N |
| D/R | 0.5053 | ambiguous | 0.558 | ambiguous | 0.127 | Stabilizing | 0.975 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/S | 0.1418 | likely_benign | 0.1623 | benign | -0.838 | Destabilizing | 0.916 | D | 0.501 | neutral | None | None | None | None | N |
| D/T | 0.2422 | likely_benign | 0.2827 | benign | -0.554 | Destabilizing | 0.975 | D | 0.636 | neutral | None | None | None | None | N |
| D/V | 0.2061 | likely_benign | 0.2309 | benign | 0.161 | Stabilizing | 0.983 | D | 0.73 | prob.delet. | N | 0.510182684 | None | None | N |
| D/W | 0.9199 | likely_pathogenic | 0.9308 | pathogenic | 0.241 | Stabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2883 | likely_benign | 0.3148 | benign | 0.279 | Stabilizing | 0.967 | D | 0.76 | deleterious | N | 0.497342258 | 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.