Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22210 | 66853;66854;66855 | chr2:178581640;178581639;178581638 | chr2:179446367;179446366;179446365 |
| N2AB | 20569 | 61930;61931;61932 | chr2:178581640;178581639;178581638 | chr2:179446367;179446366;179446365 |
| N2A | 19642 | 59149;59150;59151 | chr2:178581640;178581639;178581638 | chr2:179446367;179446366;179446365 |
| N2B | 13145 | 39658;39659;39660 | chr2:178581640;178581639;178581638 | chr2:179446367;179446366;179446365 |
| Novex-1 | 13270 | 40033;40034;40035 | chr2:178581640;178581639;178581638 | chr2:179446367;179446366;179446365 |
| Novex-2 | 13337 | 40234;40235;40236 | chr2:178581640;178581639;178581638 | chr2:179446367;179446366;179446365 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/E | None | None | None | N | 0.062 | 0.098 | 0.115124310173 | gnomAD-4.0.0 | 1.59349E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78847E-05 | None | 0 | 0 | 0 | 0 | 0 |
| Q/K | rs757047748  |
-0.329 | None | N | 0.064 | 0.113 | 0.0762999501168 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| Q/K | rs757047748 |
-0.329 | None | N | 0.064 | 0.113 | 0.0762999501168 | gnomAD-4.0.0 | 3.18699E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72397E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.1308 | likely_benign | 0.1296 | benign | -0.111 | Destabilizing | None | N | 0.131 | neutral | None | None | None | None | N |
| Q/C | 0.6411 | likely_pathogenic | 0.6362 | pathogenic | 0.122 | Stabilizing | 0.676 | D | 0.421 | neutral | None | None | None | None | N |
| Q/D | 0.2679 | likely_benign | 0.2595 | benign | -0.104 | Destabilizing | None | N | 0.071 | neutral | None | None | None | None | N |
| Q/E | 0.0697 | likely_benign | 0.0736 | benign | -0.15 | Destabilizing | None | N | 0.062 | neutral | N | 0.384164735 | None | None | N |
| Q/F | 0.6954 | likely_pathogenic | 0.6786 | pathogenic | -0.424 | Destabilizing | 0.356 | N | 0.503 | neutral | None | None | None | None | N |
| Q/G | 0.1918 | likely_benign | 0.1956 | benign | -0.258 | Destabilizing | 0.016 | N | 0.305 | neutral | None | None | None | None | N |
| Q/H | 0.2075 | likely_benign | 0.2015 | benign | -0.118 | Destabilizing | 0.295 | N | 0.321 | neutral | N | 0.449197649 | None | None | N |
| Q/I | 0.3665 | ambiguous | 0.3545 | ambiguous | 0.184 | Stabilizing | 0.072 | N | 0.534 | neutral | None | None | None | None | N |
| Q/K | 0.0671 | likely_benign | 0.0761 | benign | 0.011 | Stabilizing | None | N | 0.064 | neutral | N | 0.37906556 | None | None | N |
| Q/L | 0.1441 | likely_benign | 0.1445 | benign | 0.184 | Stabilizing | 0.012 | N | 0.332 | neutral | N | 0.434785557 | None | None | N |
| Q/M | 0.3293 | likely_benign | 0.3261 | benign | 0.269 | Stabilizing | 0.628 | D | 0.328 | neutral | None | None | None | None | N |
| Q/N | 0.2212 | likely_benign | 0.2126 | benign | -0.184 | Destabilizing | 0.016 | N | 0.237 | neutral | None | None | None | None | N |
| Q/P | 0.1187 | likely_benign | 0.1138 | benign | 0.112 | Stabilizing | 0.106 | N | 0.386 | neutral | N | 0.386954324 | None | None | N |
| Q/R | 0.093 | likely_benign | 0.1002 | benign | 0.2 | Stabilizing | 0.012 | N | 0.292 | neutral | N | 0.393474865 | None | None | N |
| Q/S | 0.1647 | likely_benign | 0.1592 | benign | -0.166 | Destabilizing | 0.007 | N | 0.195 | neutral | None | None | None | None | N |
| Q/T | 0.1583 | likely_benign | 0.1516 | benign | -0.08 | Destabilizing | 0.031 | N | 0.374 | neutral | None | None | None | None | N |
| Q/V | 0.2022 | likely_benign | 0.2003 | benign | 0.112 | Stabilizing | 0.016 | N | 0.359 | neutral | None | None | None | None | N |
| Q/W | 0.6016 | likely_pathogenic | 0.5987 | pathogenic | -0.474 | Destabilizing | 0.864 | D | 0.417 | neutral | None | None | None | None | N |
| Q/Y | 0.4827 | ambiguous | 0.4608 | ambiguous | -0.198 | Destabilizing | 0.628 | D | 0.465 | neutral | None | None | 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.