Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17723 | 53392;53393;53394 | chr2:178607521;178607520;178607519 | chr2:179472248;179472247;179472246 |
| N2AB | 16082 | 48469;48470;48471 | chr2:178607521;178607520;178607519 | chr2:179472248;179472247;179472246 |
| N2A | 15155 | 45688;45689;45690 | chr2:178607521;178607520;178607519 | chr2:179472248;179472247;179472246 |
| N2B | 8658 | 26197;26198;26199 | chr2:178607521;178607520;178607519 | chr2:179472248;179472247;179472246 |
| Novex-1 | 8783 | 26572;26573;26574 | chr2:178607521;178607520;178607519 | chr2:179472248;179472247;179472246 |
| Novex-2 | 8850 | 26773;26774;26775 | chr2:178607521;178607520;178607519 | chr2:179472248;179472247;179472246 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1420844949  |
None | 0.061 | N | 0.135 | 0.123 | 0.413241256734 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1420844949 |
None | 0.061 | N | 0.135 | 0.123 | 0.413241256734 | gnomAD-4.0.0 | 5.57955E-06 | None | None | None | None | I | None | 0 | 1.66756E-05 | None | 0 | 0 | None | 0 | 0 | 6.78333E-06 | 0 | 0 |
| V/D | rs1420844949 |
0.128 | 0.852 | N | 0.333 | 0.325 | 0.700328372174 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/D | rs1420844949 |
0.128 | 0.852 | N | 0.333 | 0.325 | 0.700328372174 | gnomAD-4.0.0 | 1.3688E-06 | None | None | None | None | I | None | 2.99133E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15955E-05 | 0 |
| V/I | rs2055183327 |
None | 0.964 | N | 0.227 | 0.178 | 0.563544018958 | gnomAD-4.0.0 | 4.10644E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87266E-05 | 0 | 1.79946E-06 | 1.15955E-05 | 3.31521E-05 |
| V/L | None | None | 0.924 | N | 0.273 | 0.213 | 0.456462010053 | gnomAD-4.0.0 | 6.84406E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99729E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1144 | likely_benign | 0.1035 | benign | -0.192 | Destabilizing | 0.061 | N | 0.135 | neutral | N | 0.439031875 | None | None | I |
| V/C | 0.6262 | likely_pathogenic | 0.6288 | pathogenic | -0.513 | Destabilizing | 0.999 | D | 0.282 | neutral | None | None | None | None | I |
| V/D | 0.1989 | likely_benign | 0.1802 | benign | -0.108 | Destabilizing | 0.852 | D | 0.333 | neutral | N | 0.433585983 | None | None | I |
| V/E | 0.1821 | likely_benign | 0.1578 | benign | -0.241 | Destabilizing | 0.079 | N | 0.197 | neutral | None | None | None | None | I |
| V/F | 0.1613 | likely_benign | 0.1461 | benign | -0.64 | Destabilizing | 0.998 | D | 0.293 | neutral | N | 0.455694839 | None | None | I |
| V/G | 0.1778 | likely_benign | 0.1711 | benign | -0.266 | Destabilizing | 0.852 | D | 0.331 | neutral | N | 0.409999834 | None | None | I |
| V/H | 0.3988 | ambiguous | 0.3848 | ambiguous | 0.015 | Stabilizing | 0.999 | D | 0.332 | neutral | None | None | None | None | I |
| V/I | 0.08 | likely_benign | 0.0759 | benign | -0.157 | Destabilizing | 0.964 | D | 0.227 | neutral | N | 0.475627394 | None | None | I |
| V/K | 0.2506 | likely_benign | 0.224 | benign | -0.117 | Destabilizing | 0.939 | D | 0.319 | neutral | None | None | None | None | I |
| V/L | 0.2031 | likely_benign | 0.1966 | benign | -0.157 | Destabilizing | 0.924 | D | 0.273 | neutral | N | 0.455348122 | None | None | I |
| V/M | 0.1597 | likely_benign | 0.1427 | benign | -0.198 | Destabilizing | 0.997 | D | 0.267 | neutral | None | None | None | None | I |
| V/N | 0.1646 | likely_benign | 0.158 | benign | 0.13 | Stabilizing | 0.991 | D | 0.371 | neutral | None | None | None | None | I |
| V/P | 0.6468 | likely_pathogenic | 0.6559 | pathogenic | -0.137 | Destabilizing | 0.991 | D | 0.357 | neutral | None | None | None | None | I |
| V/Q | 0.2258 | likely_benign | 0.2096 | benign | -0.123 | Destabilizing | 0.982 | D | 0.355 | neutral | None | None | None | None | I |
| V/R | 0.2196 | likely_benign | 0.2041 | benign | 0.326 | Stabilizing | 0.982 | D | 0.371 | neutral | None | None | None | None | I |
| V/S | 0.1373 | likely_benign | 0.128 | benign | -0.191 | Destabilizing | 0.759 | D | 0.302 | neutral | None | None | None | None | I |
| V/T | 0.1177 | likely_benign | 0.1037 | benign | -0.228 | Destabilizing | 0.17 | N | 0.173 | neutral | None | None | None | None | I |
| V/W | 0.7242 | likely_pathogenic | 0.7063 | pathogenic | -0.722 | Destabilizing | 0.999 | D | 0.372 | neutral | None | None | None | None | I |
| V/Y | 0.4629 | ambiguous | 0.4608 | ambiguous | -0.389 | Destabilizing | 0.997 | D | 0.289 | neutral | None | None | 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.