Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19569 | 58930;58931;58932 | chr2:178593595;178593594;178593593 | chr2:179458322;179458321;179458320 |
| N2AB | 17928 | 54007;54008;54009 | chr2:178593595;178593594;178593593 | chr2:179458322;179458321;179458320 |
| N2A | 17001 | 51226;51227;51228 | chr2:178593595;178593594;178593593 | chr2:179458322;179458321;179458320 |
| N2B | 10504 | 31735;31736;31737 | chr2:178593595;178593594;178593593 | chr2:179458322;179458321;179458320 |
| Novex-1 | 10629 | 32110;32111;32112 | chr2:178593595;178593594;178593593 | chr2:179458322;179458321;179458320 |
| Novex-2 | 10696 | 32311;32312;32313 | chr2:178593595;178593594;178593593 | chr2:179458322;179458321;179458320 |
| 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/N | rs397517638  |
0.353 | 0.915 | N | 0.499 | 0.203 | 0.330069100803 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 8.96E-06 | 0 |
| D/N | rs397517638 |
0.353 | 0.915 | N | 0.499 | 0.203 | 0.330069100803 | 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 |
| D/N | rs397517638 |
0.353 | 0.915 | N | 0.499 | 0.203 | 0.330069100803 | gnomAD-4.0.0 | 1.86072E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69579E-06 | 1.10135E-05 | 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 | 0.1112 | likely_benign | 0.1152 | benign | -0.058 | Destabilizing | 0.029 | N | 0.273 | neutral | N | 0.460633725 | None | None | N |
| D/C | 0.5044 | ambiguous | 0.512 | ambiguous | -0.11 | Destabilizing | 0.998 | D | 0.548 | neutral | None | None | None | None | N |
| D/E | 0.1097 | likely_benign | 0.1116 | benign | -0.18 | Destabilizing | 0.817 | D | 0.439 | neutral | N | 0.419555106 | None | None | N |
| D/F | 0.523 | ambiguous | 0.5251 | ambiguous | 0.192 | Stabilizing | 0.994 | D | 0.568 | neutral | None | None | None | None | N |
| D/G | 0.1245 | likely_benign | 0.1285 | benign | -0.25 | Destabilizing | 0.007 | N | 0.222 | neutral | N | 0.479257094 | None | None | N |
| D/H | 0.2238 | likely_benign | 0.2305 | benign | 0.628 | Stabilizing | 0.998 | D | 0.523 | neutral | N | 0.4906134 | None | None | N |
| D/I | 0.2655 | likely_benign | 0.2628 | benign | 0.399 | Stabilizing | 0.961 | D | 0.597 | neutral | None | None | None | None | N |
| D/K | 0.2028 | likely_benign | 0.228 | benign | 0.556 | Stabilizing | 0.876 | D | 0.556 | neutral | None | None | None | None | N |
| D/L | 0.275 | likely_benign | 0.2894 | benign | 0.399 | Stabilizing | 0.876 | D | 0.617 | neutral | None | None | None | None | N |
| D/M | 0.5115 | ambiguous | 0.5051 | ambiguous | 0.258 | Stabilizing | 0.998 | D | 0.549 | neutral | None | None | None | None | N |
| D/N | 0.0962 | likely_benign | 0.0956 | benign | -0.016 | Destabilizing | 0.915 | D | 0.499 | neutral | N | 0.501000267 | None | None | N |
| D/P | 0.3292 | likely_benign | 0.3645 | ambiguous | 0.268 | Stabilizing | 0.981 | D | 0.561 | neutral | None | None | None | None | N |
| D/Q | 0.222 | likely_benign | 0.2373 | benign | 0.068 | Stabilizing | 0.994 | D | 0.508 | neutral | None | None | None | None | N |
| D/R | 0.2679 | likely_benign | 0.2869 | benign | 0.81 | Stabilizing | 0.981 | D | 0.557 | neutral | None | None | None | None | N |
| D/S | 0.1002 | likely_benign | 0.1004 | benign | -0.063 | Destabilizing | 0.594 | D | 0.411 | neutral | None | None | None | None | N |
| D/T | 0.1747 | likely_benign | 0.1741 | benign | 0.112 | Stabilizing | 0.087 | N | 0.293 | neutral | None | None | None | None | N |
| D/V | 0.1514 | likely_benign | 0.1502 | benign | 0.268 | Stabilizing | 0.842 | D | 0.571 | neutral | N | 0.48974591 | None | None | N |
| D/W | 0.8419 | likely_pathogenic | 0.8501 | pathogenic | 0.347 | Stabilizing | 0.998 | D | 0.629 | neutral | None | None | None | None | N |
| D/Y | 0.1991 | likely_benign | 0.2043 | benign | 0.451 | Stabilizing | 0.991 | D | 0.565 | neutral | N | 0.491120379 | 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.