Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14205 | 42838;42839;42840 | chr2:178633886;178633885;178633884 | chr2:179498613;179498612;179498611 |
| N2AB | 12564 | 37915;37916;37917 | chr2:178633886;178633885;178633884 | chr2:179498613;179498612;179498611 |
| N2A | 11637 | 35134;35135;35136 | chr2:178633886;178633885;178633884 | chr2:179498613;179498612;179498611 |
| N2B | 5140 | 15643;15644;15645 | chr2:178633886;178633885;178633884 | chr2:179498613;179498612;179498611 |
| Novex-1 | 5265 | 16018;16019;16020 | chr2:178633886;178633885;178633884 | chr2:179498613;179498612;179498611 |
| Novex-2 | 5332 | 16219;16220;16221 | chr2:178633886;178633885;178633884 | chr2:179498613;179498612;179498611 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/V | rs747480084  |
-0.353 | 0.201 | N | 0.385 | 0.046 | 0.293147016451 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| L/V | rs747480084 |
-0.353 | 0.201 | N | 0.385 | 0.046 | 0.293147016451 | gnomAD-4.0.0 | 1.36869E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79921E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4922 | ambiguous | 0.3949 | ambiguous | -0.902 | Destabilizing | 0.25 | N | 0.376 | neutral | None | None | None | None | N |
| L/C | 0.8765 | likely_pathogenic | 0.8162 | pathogenic | -0.654 | Destabilizing | 0.982 | D | 0.419 | neutral | None | None | None | None | N |
| L/D | 0.9286 | likely_pathogenic | 0.8948 | pathogenic | -0.371 | Destabilizing | 0.7 | D | 0.547 | neutral | None | None | None | None | N |
| L/E | 0.6681 | likely_pathogenic | 0.6325 | pathogenic | -0.452 | Destabilizing | 0.7 | D | 0.557 | neutral | None | None | None | None | N |
| L/F | 0.4189 | ambiguous | 0.3321 | benign | -0.809 | Destabilizing | 0.638 | D | 0.319 | neutral | N | 0.468877891 | None | None | N |
| L/G | 0.8328 | likely_pathogenic | 0.7627 | pathogenic | -1.099 | Destabilizing | 0.7 | D | 0.553 | neutral | None | None | None | None | N |
| L/H | 0.6354 | likely_pathogenic | 0.5355 | ambiguous | -0.325 | Destabilizing | 0.982 | D | 0.564 | neutral | None | None | None | None | N |
| L/I | 0.1762 | likely_benign | 0.1392 | benign | -0.491 | Destabilizing | 0.25 | N | 0.356 | neutral | None | None | None | None | N |
| L/K | 0.4073 | ambiguous | 0.3724 | ambiguous | -0.536 | Destabilizing | 0.7 | D | 0.445 | neutral | None | None | None | None | N |
| L/M | 0.2156 | likely_benign | 0.157 | benign | -0.449 | Destabilizing | 0.015 | N | 0.233 | neutral | N | 0.470275751 | None | None | N |
| L/N | 0.7688 | likely_pathogenic | 0.6864 | pathogenic | -0.307 | Destabilizing | 0.826 | D | 0.558 | neutral | None | None | None | None | N |
| L/P | 0.6021 | likely_pathogenic | 0.5015 | ambiguous | -0.594 | Destabilizing | 0.005 | N | 0.373 | neutral | None | None | None | None | N |
| L/Q | 0.4104 | ambiguous | 0.3484 | ambiguous | -0.547 | Destabilizing | 0.7 | D | 0.478 | neutral | None | None | None | None | N |
| L/R | 0.3698 | ambiguous | 0.3486 | ambiguous | 0.074 | Stabilizing | 0.7 | D | 0.475 | neutral | None | None | None | None | N |
| L/S | 0.6631 | likely_pathogenic | 0.5089 | ambiguous | -0.79 | Destabilizing | 0.638 | D | 0.397 | neutral | N | 0.440615593 | None | None | N |
| L/T | 0.4728 | ambiguous | 0.364 | ambiguous | -0.76 | Destabilizing | 0.7 | D | 0.302 | neutral | None | None | None | None | N |
| L/V | 0.1955 | likely_benign | 0.1606 | benign | -0.594 | Destabilizing | 0.201 | N | 0.385 | neutral | N | 0.440072812 | None | None | N |
| L/W | 0.6044 | likely_pathogenic | 0.4919 | ambiguous | -0.813 | Destabilizing | 0.976 | D | 0.549 | neutral | D | 0.593583172 | None | None | N |
| L/Y | 0.7616 | likely_pathogenic | 0.6775 | pathogenic | -0.579 | Destabilizing | 0.826 | D | 0.379 | 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.