Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21488 | 64687;64688;64689 | chr2:178585282;178585281;178585280 | chr2:179450009;179450008;179450007 |
| N2AB | 19847 | 59764;59765;59766 | chr2:178585282;178585281;178585280 | chr2:179450009;179450008;179450007 |
| N2A | 18920 | 56983;56984;56985 | chr2:178585282;178585281;178585280 | chr2:179450009;179450008;179450007 |
| N2B | 12423 | 37492;37493;37494 | chr2:178585282;178585281;178585280 | chr2:179450009;179450008;179450007 |
| Novex-1 | 12548 | 37867;37868;37869 | chr2:178585282;178585281;178585280 | chr2:179450009;179450008;179450007 |
| Novex-2 | 12615 | 38068;38069;38070 | chr2:178585282;178585281;178585280 | chr2:179450009;179450008;179450007 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 1.0 | N | 0.903 | 0.459 | 0.56713362702 | gnomAD-4.0.0 | 2.40065E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62501E-06 | 0 | 0 |
| A/S | rs374992146  |
-1.711 | 1.0 | N | 0.712 | 0.413 | 0.374255764437 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.665E-04 |
| A/S | rs374992146 |
-1.711 | 1.0 | N | 0.712 | 0.413 | 0.374255764437 | gnomAD-4.0.0 | 1.59512E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86403E-06 | 0 | 0 |
| A/T | rs374992146 |
-1.48 | 1.0 | N | 0.871 | 0.387 | 0.381071309025 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 0 |
| A/T | rs374992146 |
-1.48 | 1.0 | N | 0.871 | 0.387 | 0.381071309025 | gnomAD-4.0.0 | 1.59512E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43951E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7234 | likely_pathogenic | 0.6815 | pathogenic | -1.244 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| A/D | 0.9949 | likely_pathogenic | 0.9913 | pathogenic | -2.647 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | N | 0.487914606 | None | None | N |
| A/E | 0.9944 | likely_pathogenic | 0.9905 | pathogenic | -2.452 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| A/F | 0.9598 | likely_pathogenic | 0.9468 | pathogenic | -0.886 | Destabilizing | 1.0 | D | 0.918 | deleterious | None | None | None | None | N |
| A/G | 0.1812 | likely_benign | 0.1348 | benign | -1.803 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.461163071 | None | None | N |
| A/H | 0.9962 | likely_pathogenic | 0.9939 | pathogenic | -2.264 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| A/I | 0.852 | likely_pathogenic | 0.8176 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| A/K | 0.9984 | likely_pathogenic | 0.9972 | pathogenic | -1.488 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| A/L | 0.8146 | likely_pathogenic | 0.7591 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| A/M | 0.8528 | likely_pathogenic | 0.8186 | pathogenic | -0.129 | Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| A/N | 0.9831 | likely_pathogenic | 0.9736 | pathogenic | -1.76 | Destabilizing | 1.0 | D | 0.912 | deleterious | None | None | None | None | N |
| A/P | 0.9845 | likely_pathogenic | 0.9751 | pathogenic | -0.422 | Destabilizing | 1.0 | D | 0.885 | deleterious | N | 0.487914606 | None | None | N |
| A/Q | 0.9912 | likely_pathogenic | 0.9868 | pathogenic | -1.574 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| A/R | 0.9958 | likely_pathogenic | 0.9934 | pathogenic | -1.507 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| A/S | 0.3515 | ambiguous | 0.3086 | benign | -2.154 | Highly Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.487407627 | None | None | N |
| A/T | 0.5384 | ambiguous | 0.4702 | ambiguous | -1.84 | Destabilizing | 1.0 | D | 0.871 | deleterious | N | 0.460656092 | None | None | N |
| A/V | 0.5524 | ambiguous | 0.5069 | ambiguous | -0.422 | Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.462382298 | None | None | N |
| A/W | 0.9975 | likely_pathogenic | 0.996 | pathogenic | -1.712 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| A/Y | 0.9877 | likely_pathogenic | 0.981 | pathogenic | -1.183 | Destabilizing | 1.0 | D | 0.929 | deleterious | 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.