Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17017 | 51274;51275;51276 | chr2:178611080;178611079;178611078 | chr2:179475807;179475806;179475805 |
| N2AB | 15376 | 46351;46352;46353 | chr2:178611080;178611079;178611078 | chr2:179475807;179475806;179475805 |
| N2A | 14449 | 43570;43571;43572 | chr2:178611080;178611079;178611078 | chr2:179475807;179475806;179475805 |
| N2B | 7952 | 24079;24080;24081 | chr2:178611080;178611079;178611078 | chr2:179475807;179475806;179475805 |
| Novex-1 | 8077 | 24454;24455;24456 | chr2:178611080;178611079;178611078 | chr2:179475807;179475806;179475805 |
| Novex-2 | 8144 | 24655;24656;24657 | chr2:178611080;178611079;178611078 | chr2:179475807;179475806;179475805 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs766949350  |
-0.74 | 0.001 | N | 0.169 | 0.121 | 0.115124310173 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/G | rs766949350 |
-0.74 | 0.001 | N | 0.169 | 0.121 | 0.115124310173 | 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 |
| S/G | rs766949350 |
-0.74 | 0.001 | N | 0.169 | 0.121 | 0.115124310173 | gnomAD-4.0.0 | 3.84787E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.18866E-06 | 0 | 0 |
| S/R | rs1246257248 |
None | 0.773 | N | 0.649 | 0.242 | 0.367803931526 | gnomAD-4.0.0 | 6.8457E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52691E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0594 | likely_benign | 0.0684 | benign | -0.896 | Destabilizing | 0.001 | N | 0.16 | neutral | None | None | None | None | N |
| S/C | 0.0751 | likely_benign | 0.087 | benign | -1.215 | Destabilizing | 0.001 | N | 0.339 | neutral | N | 0.442042164 | None | None | N |
| S/D | 0.9692 | likely_pathogenic | 0.9688 | pathogenic | -2.165 | Highly Destabilizing | 0.388 | N | 0.507 | neutral | None | None | None | None | N |
| S/E | 0.9718 | likely_pathogenic | 0.9692 | pathogenic | -2.044 | Highly Destabilizing | 0.388 | N | 0.51 | neutral | None | None | None | None | N |
| S/F | 0.8599 | likely_pathogenic | 0.9087 | pathogenic | -0.918 | Destabilizing | 0.818 | D | 0.638 | neutral | None | None | None | None | N |
| S/G | 0.184 | likely_benign | 0.2125 | benign | -1.173 | Destabilizing | 0.001 | N | 0.169 | neutral | N | 0.511544991 | None | None | N |
| S/H | 0.96 | likely_pathogenic | 0.9595 | pathogenic | -1.458 | Destabilizing | 0.981 | D | 0.584 | neutral | None | None | None | None | N |
| S/I | 0.3538 | ambiguous | 0.4443 | ambiguous | -0.232 | Destabilizing | 0.324 | N | 0.632 | neutral | N | 0.467606543 | None | None | N |
| S/K | 0.995 | likely_pathogenic | 0.9947 | pathogenic | -0.782 | Destabilizing | 0.388 | N | 0.501 | neutral | None | None | None | None | N |
| S/L | 0.2849 | likely_benign | 0.3715 | ambiguous | -0.232 | Destabilizing | 0.388 | N | 0.523 | neutral | None | None | None | None | N |
| S/M | 0.4404 | ambiguous | 0.5157 | ambiguous | -0.35 | Destabilizing | 0.932 | D | 0.595 | neutral | None | None | None | None | N |
| S/N | 0.6828 | likely_pathogenic | 0.7037 | pathogenic | -1.343 | Destabilizing | 0.324 | N | 0.529 | neutral | D | 0.58556516 | None | None | N |
| S/P | 0.6589 | likely_pathogenic | 0.584 | pathogenic | -0.422 | Destabilizing | 0.818 | D | 0.655 | neutral | None | None | None | None | N |
| S/Q | 0.9689 | likely_pathogenic | 0.9672 | pathogenic | -1.359 | Destabilizing | 0.818 | D | 0.577 | neutral | None | None | None | None | N |
| S/R | 0.9882 | likely_pathogenic | 0.9882 | pathogenic | -0.784 | Destabilizing | 0.773 | D | 0.649 | neutral | N | 0.50306955 | None | None | N |
| S/T | 0.0815 | likely_benign | 0.1003 | benign | -1.02 | Destabilizing | 0.006 | N | 0.177 | neutral | N | 0.482466204 | None | None | N |
| S/V | 0.2115 | likely_benign | 0.2661 | benign | -0.422 | Destabilizing | 0.241 | N | 0.519 | neutral | None | None | None | None | N |
| S/W | 0.9611 | likely_pathogenic | 0.9661 | pathogenic | -1.128 | Destabilizing | 0.981 | D | 0.599 | neutral | None | None | None | None | N |
| S/Y | 0.879 | likely_pathogenic | 0.9008 | pathogenic | -0.715 | Destabilizing | 0.932 | D | 0.625 | 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.