Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19337 | 58234;58235;58236 | chr2:178594485;178594484;178594483 | chr2:179459212;179459211;179459210 |
| N2AB | 17696 | 53311;53312;53313 | chr2:178594485;178594484;178594483 | chr2:179459212;179459211;179459210 |
| N2A | 16769 | 50530;50531;50532 | chr2:178594485;178594484;178594483 | chr2:179459212;179459211;179459210 |
| N2B | 10272 | 31039;31040;31041 | chr2:178594485;178594484;178594483 | chr2:179459212;179459211;179459210 |
| Novex-1 | 10397 | 31414;31415;31416 | chr2:178594485;178594484;178594483 | chr2:179459212;179459211;179459210 |
| Novex-2 | 10464 | 31615;31616;31617 | chr2:178594485;178594484;178594483 | chr2:179459212;179459211;179459210 |
| 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/E | None | None | 0.005 | N | 0.124 | 0.071 | 0.136095386433 | gnomAD-4.0.0 | 3.1844E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76872E-05 | 0 | None | 0 | 0 | 0 | 1.43349E-05 | 0 |
| D/N | rs1239348052  |
0.348 | 0.801 | N | 0.471 | 0.27 | 0.218112801441 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| D/N | rs1239348052 |
0.348 | 0.801 | N | 0.471 | 0.27 | 0.218112801441 | gnomAD-4.0.0 | 1.59223E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86007E-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 | 0.1793 | likely_benign | 0.1433 | benign | 0.079 | Stabilizing | 0.801 | D | 0.438 | neutral | N | 0.453854107 | None | None | N |
| D/C | 0.6094 | likely_pathogenic | 0.4847 | ambiguous | 0.263 | Stabilizing | 0.998 | D | 0.519 | neutral | None | None | None | None | N |
| D/E | 0.1148 | likely_benign | 0.1127 | benign | -0.115 | Destabilizing | 0.005 | N | 0.124 | neutral | N | 0.434652271 | None | None | N |
| D/F | 0.6867 | likely_pathogenic | 0.5809 | pathogenic | -0.147 | Destabilizing | 0.991 | D | 0.496 | neutral | None | None | None | None | N |
| D/G | 0.1552 | likely_benign | 0.1126 | benign | -0.032 | Destabilizing | 0.801 | D | 0.417 | neutral | N | 0.491198987 | None | None | N |
| D/H | 0.2936 | likely_benign | 0.2085 | benign | 0.203 | Stabilizing | 0.991 | D | 0.401 | neutral | D | 0.525196917 | None | None | N |
| D/I | 0.4081 | ambiguous | 0.3143 | benign | 0.299 | Stabilizing | 0.949 | D | 0.512 | neutral | None | None | None | None | N |
| D/K | 0.2877 | likely_benign | 0.2043 | benign | 0.613 | Stabilizing | 0.728 | D | 0.399 | neutral | None | None | None | None | N |
| D/L | 0.4563 | ambiguous | 0.3603 | ambiguous | 0.299 | Stabilizing | 0.842 | D | 0.477 | neutral | None | None | None | None | N |
| D/M | 0.5938 | likely_pathogenic | 0.5235 | ambiguous | 0.31 | Stabilizing | 0.998 | D | 0.49 | neutral | None | None | None | None | N |
| D/N | 0.1004 | likely_benign | 0.0867 | benign | 0.553 | Stabilizing | 0.801 | D | 0.471 | neutral | N | 0.495490086 | None | None | N |
| D/P | 0.6451 | likely_pathogenic | 0.5543 | ambiguous | 0.246 | Stabilizing | 0.974 | D | 0.386 | neutral | None | None | None | None | N |
| D/Q | 0.2573 | likely_benign | 0.2085 | benign | 0.534 | Stabilizing | 0.904 | D | 0.365 | neutral | None | None | None | None | N |
| D/R | 0.3668 | ambiguous | 0.2615 | benign | 0.675 | Stabilizing | 0.949 | D | 0.437 | neutral | None | None | None | None | N |
| D/S | 0.1274 | likely_benign | 0.105 | benign | 0.426 | Stabilizing | 0.728 | D | 0.419 | neutral | None | None | None | None | N |
| D/T | 0.2002 | likely_benign | 0.1645 | benign | 0.51 | Stabilizing | 0.029 | N | 0.195 | neutral | None | None | None | None | N |
| D/V | 0.2619 | likely_benign | 0.1965 | benign | 0.246 | Stabilizing | 0.801 | D | 0.469 | neutral | N | 0.463724384 | None | None | N |
| D/W | 0.8886 | likely_pathogenic | 0.823 | pathogenic | -0.148 | Destabilizing | 0.998 | D | 0.608 | neutral | None | None | None | None | N |
| D/Y | 0.3287 | likely_benign | 0.2274 | benign | 0.073 | Stabilizing | 0.989 | D | 0.495 | neutral | N | 0.481638141 | 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.