Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30098 | 90517;90518;90519 | chr2:178552608;178552607;178552606 | chr2:179417335;179417334;179417333 |
| N2AB | 28457 | 85594;85595;85596 | chr2:178552608;178552607;178552606 | chr2:179417335;179417334;179417333 |
| N2A | 27530 | 82813;82814;82815 | chr2:178552608;178552607;178552606 | chr2:179417335;179417334;179417333 |
| N2B | 21033 | 63322;63323;63324 | chr2:178552608;178552607;178552606 | chr2:179417335;179417334;179417333 |
| Novex-1 | 21158 | 63697;63698;63699 | chr2:178552608;178552607;178552606 | chr2:179417335;179417334;179417333 |
| Novex-2 | 21225 | 63898;63899;63900 | chr2:178552608;178552607;178552606 | chr2:179417335;179417334;179417333 |
| 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/F | rs1221691128  |
-0.983 | 0.188 | N | 0.468 | 0.076 | 0.434825671192 | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.29634E-04 | 0 |
| V/F | rs1221691128 |
-0.983 | 0.188 | N | 0.468 | 0.076 | 0.434825671192 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/F | rs1221691128 |
-0.983 | 0.188 | N | 0.468 | 0.076 | 0.434825671192 | gnomAD-4.0.0 | 8.67536E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01709E-05 | 0 | 3.20195E-05 |
| V/I | None | None | None | N | 0.239 | 0.052 | 0.180583059064 | gnomAD-4.0.0 | 2.05254E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79887E-06 | 1.15937E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1345 | likely_benign | 0.1153 | benign | -0.851 | Destabilizing | 0.027 | N | 0.383 | neutral | N | 0.457507701 | None | None | N |
| V/C | 0.6749 | likely_pathogenic | 0.6106 | pathogenic | -0.677 | Destabilizing | 0.935 | D | 0.453 | neutral | None | None | None | None | N |
| V/D | 0.2023 | likely_benign | 0.1599 | benign | -0.378 | Destabilizing | 0.062 | N | 0.534 | neutral | N | 0.449618936 | None | None | N |
| V/E | 0.1265 | likely_benign | 0.1034 | benign | -0.453 | Destabilizing | 0.001 | N | 0.318 | neutral | None | None | None | None | N |
| V/F | 0.1874 | likely_benign | 0.1526 | benign | -0.809 | Destabilizing | 0.188 | N | 0.468 | neutral | N | 0.492852425 | None | None | N |
| V/G | 0.2093 | likely_benign | 0.1663 | benign | -1.07 | Destabilizing | 0.117 | N | 0.537 | neutral | N | 0.47374659 | None | None | N |
| V/H | 0.4785 | ambiguous | 0.4046 | ambiguous | -0.644 | Destabilizing | 0.824 | D | 0.556 | neutral | None | None | None | None | N |
| V/I | 0.0708 | likely_benign | 0.0676 | benign | -0.396 | Destabilizing | None | N | 0.239 | neutral | N | 0.459817287 | None | None | N |
| V/K | 0.2937 | likely_benign | 0.2389 | benign | -0.687 | Destabilizing | 0.081 | N | 0.484 | neutral | None | None | None | None | N |
| V/L | 0.1517 | likely_benign | 0.1269 | benign | -0.396 | Destabilizing | None | N | 0.112 | neutral | N | 0.468551414 | None | None | N |
| V/M | 0.1105 | likely_benign | 0.1003 | benign | -0.326 | Destabilizing | 0.035 | N | 0.355 | neutral | None | None | None | None | N |
| V/N | 0.1705 | likely_benign | 0.1447 | benign | -0.37 | Destabilizing | 0.38 | N | 0.553 | neutral | None | None | None | None | N |
| V/P | 0.3958 | ambiguous | 0.3026 | benign | -0.511 | Destabilizing | 0.555 | D | 0.524 | neutral | None | None | None | None | N |
| V/Q | 0.2102 | likely_benign | 0.1716 | benign | -0.593 | Destabilizing | 0.235 | N | 0.525 | neutral | None | None | None | None | N |
| V/R | 0.3376 | likely_benign | 0.2643 | benign | -0.192 | Destabilizing | 0.235 | N | 0.553 | neutral | None | None | None | None | N |
| V/S | 0.146 | likely_benign | 0.1266 | benign | -0.849 | Destabilizing | 0.081 | N | 0.467 | neutral | None | None | None | None | N |
| V/T | 0.119 | likely_benign | 0.1085 | benign | -0.817 | Destabilizing | 0.002 | N | 0.211 | neutral | None | None | None | None | N |
| V/W | 0.8057 | likely_pathogenic | 0.7302 | pathogenic | -0.908 | Destabilizing | 0.935 | D | 0.599 | neutral | None | None | None | None | N |
| V/Y | 0.4877 | ambiguous | 0.4194 | ambiguous | -0.618 | Destabilizing | 0.555 | D | 0.475 | 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.