Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17754 | 53485;53486;53487 | chr2:178607428;178607427;178607426 | chr2:179472155;179472154;179472153 |
| N2AB | 16113 | 48562;48563;48564 | chr2:178607428;178607427;178607426 | chr2:179472155;179472154;179472153 |
| N2A | 15186 | 45781;45782;45783 | chr2:178607428;178607427;178607426 | chr2:179472155;179472154;179472153 |
| N2B | 8689 | 26290;26291;26292 | chr2:178607428;178607427;178607426 | chr2:179472155;179472154;179472153 |
| Novex-1 | 8814 | 26665;26666;26667 | chr2:178607428;178607427;178607426 | chr2:179472155;179472154;179472153 |
| Novex-2 | 8881 | 26866;26867;26868 | chr2:178607428;178607427;178607426 | chr2:179472155;179472154;179472153 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs397517612  |
-0.471 | 0.024 | N | 0.3 | 0.172 | 0.236278675362 | gnomAD-2.1.1 | 7.936E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.96169E-03 | None | 0 | 5.48E-05 | 2.81057E-04 |
| F/L | rs397517612 |
-0.471 | 0.024 | N | 0.3 | 0.172 | 0.236278675362 | gnomAD-3.1.2 | 1.64441E-04 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 4.96483E-03 | 0 |
| F/L | rs397517612 |
-0.471 | 0.024 | N | 0.3 | 0.172 | 0.236278675362 | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| F/L | rs397517612 |
-0.471 | 0.024 | N | 0.3 | 0.172 | 0.236278675362 | gnomAD-4.0.0 | 3.57058E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.65289E-04 | 4.23949E-06 | 5.96271E-03 | 4.32401E-04 |
| F/S | rs749312983 |
-0.712 | None | N | 0.169 | 0.103 | 0.362758974969 | gnomAD-2.1.1 | 1.46566E-04 | None | None | None | None | I | None | 4.14E-05 | 1.07563E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 2.81057E-04 |
| F/S | rs749312983 |
-0.712 | None | N | 0.169 | 0.103 | 0.362758974969 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 4.83E-05 | 1.31182E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs749312983 |
-0.712 | None | N | 0.169 | 0.103 | 0.362758974969 | gnomAD-4.0.0 | 3.16146E-05 | None | None | None | None | I | None | 4.00021E-05 | 7.6705E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20297E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.3544 | ambiguous | 0.1587 | benign | -0.914 | Destabilizing | 0.003 | N | 0.285 | neutral | None | None | None | None | I |
| F/C | 0.4012 | ambiguous | 0.2205 | benign | -0.326 | Destabilizing | 0.295 | N | 0.416 | neutral | N | 0.445381844 | None | None | I |
| F/D | 0.6377 | likely_pathogenic | 0.4063 | ambiguous | 0.647 | Stabilizing | 0.016 | N | 0.36 | neutral | None | None | None | None | I |
| F/E | 0.6324 | likely_pathogenic | 0.4233 | ambiguous | 0.624 | Stabilizing | 0.016 | N | 0.385 | neutral | None | None | None | None | I |
| F/G | 0.6958 | likely_pathogenic | 0.4315 | ambiguous | -1.105 | Destabilizing | None | N | 0.244 | neutral | None | None | None | None | I |
| F/H | 0.492 | ambiguous | 0.3218 | benign | 0.253 | Stabilizing | 0.214 | N | 0.415 | neutral | None | None | None | None | I |
| F/I | 0.263 | likely_benign | 0.1495 | benign | -0.429 | Destabilizing | 0.055 | N | 0.344 | neutral | N | 0.428334879 | None | None | I |
| F/K | 0.71 | likely_pathogenic | 0.5221 | ambiguous | -0.127 | Destabilizing | 0.016 | N | 0.381 | neutral | None | None | None | None | I |
| F/L | 0.8673 | likely_pathogenic | 0.6849 | pathogenic | -0.429 | Destabilizing | 0.024 | N | 0.3 | neutral | N | 0.441186746 | None | None | I |
| F/M | 0.4138 | ambiguous | 0.2775 | benign | -0.392 | Destabilizing | 0.628 | D | 0.38 | neutral | None | None | None | None | I |
| F/N | 0.4098 | ambiguous | 0.2315 | benign | -0.101 | Destabilizing | None | N | 0.275 | neutral | None | None | None | None | I |
| F/P | 0.9785 | likely_pathogenic | 0.9055 | pathogenic | -0.572 | Destabilizing | 0.072 | N | 0.503 | neutral | None | None | None | None | I |
| F/Q | 0.5995 | likely_pathogenic | 0.4079 | ambiguous | -0.153 | Destabilizing | 0.072 | N | 0.504 | neutral | None | None | None | None | I |
| F/R | 0.6984 | likely_pathogenic | 0.498 | ambiguous | 0.323 | Stabilizing | 0.072 | N | 0.482 | neutral | None | None | None | None | I |
| F/S | 0.2013 | likely_benign | 0.0883 | benign | -0.744 | Destabilizing | None | N | 0.169 | neutral | N | 0.335403288 | None | None | I |
| F/T | 0.2086 | likely_benign | 0.1128 | benign | -0.675 | Destabilizing | 0.016 | N | 0.334 | neutral | None | None | None | None | I |
| F/V | 0.2086 | likely_benign | 0.119 | benign | -0.572 | Destabilizing | 0.024 | N | 0.381 | neutral | N | 0.400686918 | None | None | I |
| F/W | 0.5753 | likely_pathogenic | 0.4124 | ambiguous | -0.253 | Destabilizing | 0.864 | D | 0.409 | neutral | None | None | None | None | I |
| F/Y | 0.1404 | likely_benign | 0.1162 | benign | -0.244 | Destabilizing | 0.106 | N | 0.409 | neutral | N | 0.418272601 | 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.