Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14641 | 44146;44147;44148 | chr2:178631127;178631126;178631125 | chr2:179495854;179495853;179495852 |
| N2AB | 13000 | 39223;39224;39225 | chr2:178631127;178631126;178631125 | chr2:179495854;179495853;179495852 |
| N2A | 12073 | 36442;36443;36444 | chr2:178631127;178631126;178631125 | chr2:179495854;179495853;179495852 |
| N2B | 5576 | 16951;16952;16953 | chr2:178631127;178631126;178631125 | chr2:179495854;179495853;179495852 |
| Novex-1 | 5701 | 17326;17327;17328 | chr2:178631127;178631126;178631125 | chr2:179495854;179495853;179495852 |
| Novex-2 | 5768 | 17527;17528;17529 | chr2:178631127;178631126;178631125 | chr2:179495854;179495853;179495852 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs2059746985  |
None | None | N | 0.173 | 0.137 | 0.298056030225 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/I | rs2059746985 |
None | None | N | 0.173 | 0.137 | 0.298056030225 | gnomAD-4.0.0 | 6.57557E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47076E-05 | 0 | 0 |
| M/K | rs1481001987 |
-1.532 | 0.055 | N | 0.535 | 0.272 | 0.57047621783 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| M/K | rs1481001987 |
-1.532 | 0.055 | N | 0.535 | 0.272 | 0.57047621783 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85951E-06 | 0 | 0 |
| M/R | None | None | 0.106 | N | 0.573 | 0.292 | 0.579790155161 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85951E-06 | 0 | 0 |
| M/V | None | None | None | N | 0.157 | 0.107 | 0.410734915765 | gnomAD-4.0.0 | 2.05318E-06 | None | None | None | None | N | None | 2.98954E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79919E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5504 | ambiguous | 0.5211 | ambiguous | -2.814 | Highly Destabilizing | 0.007 | N | 0.408 | neutral | None | None | None | None | N |
| M/C | 0.7892 | likely_pathogenic | 0.7906 | pathogenic | -2.335 | Highly Destabilizing | 0.628 | D | 0.567 | neutral | None | None | None | None | N |
| M/D | 0.9045 | likely_pathogenic | 0.9149 | pathogenic | -2.461 | Highly Destabilizing | 0.072 | N | 0.57 | neutral | None | None | None | None | N |
| M/E | 0.5459 | ambiguous | 0.5622 | ambiguous | -2.277 | Highly Destabilizing | 0.072 | N | 0.53 | neutral | None | None | None | None | N |
| M/F | 0.3296 | likely_benign | 0.3331 | benign | -1.233 | Destabilizing | 0.072 | N | 0.49 | neutral | None | None | None | None | N |
| M/G | 0.7926 | likely_pathogenic | 0.7782 | pathogenic | -3.234 | Highly Destabilizing | 0.031 | N | 0.509 | neutral | None | None | None | None | N |
| M/H | 0.5877 | likely_pathogenic | 0.5971 | pathogenic | -2.698 | Highly Destabilizing | 0.628 | D | 0.557 | neutral | None | None | None | None | N |
| M/I | 0.1886 | likely_benign | 0.2319 | benign | -1.603 | Destabilizing | None | N | 0.173 | neutral | N | 0.347023579 | None | None | N |
| M/K | 0.2734 | likely_benign | 0.2911 | benign | -1.958 | Destabilizing | 0.055 | N | 0.535 | neutral | N | 0.431101471 | None | None | N |
| M/L | 0.1393 | likely_benign | 0.1445 | benign | -1.603 | Destabilizing | 0.001 | N | 0.23 | neutral | N | 0.466499773 | None | None | N |
| M/N | 0.581 | likely_pathogenic | 0.611 | pathogenic | -2.145 | Highly Destabilizing | 0.072 | N | 0.561 | neutral | None | None | None | None | N |
| M/P | 0.9851 | likely_pathogenic | 0.9869 | pathogenic | -1.992 | Destabilizing | 0.325 | N | 0.577 | neutral | None | None | None | None | N |
| M/Q | 0.3209 | likely_benign | 0.3279 | benign | -1.945 | Destabilizing | 0.136 | N | 0.519 | neutral | None | None | None | None | N |
| M/R | 0.2875 | likely_benign | 0.2999 | benign | -1.784 | Destabilizing | 0.106 | N | 0.573 | neutral | N | 0.423090784 | None | None | N |
| M/S | 0.5114 | ambiguous | 0.4885 | ambiguous | -2.714 | Highly Destabilizing | 0.001 | N | 0.312 | neutral | None | None | None | None | N |
| M/T | 0.2871 | likely_benign | 0.2777 | benign | -2.43 | Highly Destabilizing | 0.024 | N | 0.477 | neutral | N | 0.407076599 | None | None | N |
| M/V | 0.1105 | likely_benign | 0.112 | benign | -1.992 | Destabilizing | None | N | 0.157 | neutral | N | 0.445571574 | None | None | N |
| M/W | 0.6483 | likely_pathogenic | 0.646 | pathogenic | -1.506 | Destabilizing | 0.864 | D | 0.563 | neutral | None | None | None | None | N |
| M/Y | 0.5549 | ambiguous | 0.5733 | pathogenic | -1.602 | Destabilizing | 0.136 | N | 0.602 | 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.