Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16891 | 50896;50897;50898 | chr2:178611558;178611557;178611556 | chr2:179476285;179476284;179476283 |
| N2AB | 15250 | 45973;45974;45975 | chr2:178611558;178611557;178611556 | chr2:179476285;179476284;179476283 |
| N2A | 14323 | 43192;43193;43194 | chr2:178611558;178611557;178611556 | chr2:179476285;179476284;179476283 |
| N2B | 7826 | 23701;23702;23703 | chr2:178611558;178611557;178611556 | chr2:179476285;179476284;179476283 |
| Novex-1 | 7951 | 24076;24077;24078 | chr2:178611558;178611557;178611556 | chr2:179476285;179476284;179476283 |
| Novex-2 | 8018 | 24277;24278;24279 | chr2:178611558;178611557;178611556 | chr2:179476285;179476284;179476283 |
| 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 | rs767149312  |
-0.637 | 0.454 | N | 0.677 | 0.142 | 0.405422107966 | gnomAD-2.1.1 | 7.17E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 7.99E-05 | 0 | 0 |
| M/I | rs767149312 |
-0.637 | 0.454 | N | 0.677 | 0.142 | 0.405422107966 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88288E-04 | 0 | 0 | 0 | 0 |
| M/I | rs767149312 |
-0.637 | 0.454 | N | 0.677 | 0.142 | 0.405422107966 | gnomAD-4.0.0 | 3.84698E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.70677E-05 | 0 | 0 | 0 | 0 |
| M/V | rs929462574 |
None | 0.454 | N | 0.461 | 0.186 | 0.388653054685 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs929462574 |
None | 0.454 | N | 0.461 | 0.186 | 0.388653054685 | gnomAD-4.0.0 | 3.0453E-06 | None | None | None | None | N | None | 1.74746E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.4101E-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 | 0.908 | likely_pathogenic | 0.9005 | pathogenic | -2.506 | Highly Destabilizing | 0.007 | N | 0.445 | neutral | None | None | None | None | N |
| M/C | 0.9339 | likely_pathogenic | 0.9388 | pathogenic | -2.447 | Highly Destabilizing | 0.991 | D | 0.785 | deleterious | None | None | None | None | N |
| M/D | 0.9991 | likely_pathogenic | 0.9984 | pathogenic | -2.3 | Highly Destabilizing | 0.974 | D | 0.814 | deleterious | None | None | None | None | N |
| M/E | 0.9832 | likely_pathogenic | 0.9766 | pathogenic | -2.045 | Highly Destabilizing | 0.842 | D | 0.771 | deleterious | None | None | None | None | N |
| M/F | 0.6251 | likely_pathogenic | 0.6197 | pathogenic | -0.93 | Destabilizing | 0.842 | D | 0.791 | deleterious | None | None | None | None | N |
| M/G | 0.9836 | likely_pathogenic | 0.9794 | pathogenic | -3.001 | Highly Destabilizing | 0.728 | D | 0.769 | deleterious | None | None | None | None | N |
| M/H | 0.9794 | likely_pathogenic | 0.9685 | pathogenic | -2.585 | Highly Destabilizing | 0.998 | D | 0.776 | deleterious | None | None | None | None | N |
| M/I | 0.6934 | likely_pathogenic | 0.6852 | pathogenic | -1.057 | Destabilizing | 0.454 | N | 0.677 | prob.neutral | N | 0.473530591 | None | None | N |
| M/K | 0.8541 | likely_pathogenic | 0.8067 | pathogenic | -1.68 | Destabilizing | 0.801 | D | 0.753 | deleterious | N | 0.454956031 | None | None | N |
| M/L | 0.252 | likely_benign | 0.2457 | benign | -1.057 | Destabilizing | 0.002 | N | 0.229 | neutral | N | 0.460295546 | None | None | N |
| M/N | 0.9888 | likely_pathogenic | 0.9809 | pathogenic | -2.109 | Highly Destabilizing | 0.974 | D | 0.799 | deleterious | None | None | None | None | N |
| M/P | 0.9996 | likely_pathogenic | 0.9994 | pathogenic | -1.526 | Destabilizing | 0.974 | D | 0.795 | deleterious | None | None | None | None | N |
| M/Q | 0.8877 | likely_pathogenic | 0.854 | pathogenic | -1.763 | Destabilizing | 0.974 | D | 0.795 | deleterious | None | None | None | None | N |
| M/R | 0.8795 | likely_pathogenic | 0.8411 | pathogenic | -1.767 | Destabilizing | 0.966 | D | 0.804 | deleterious | N | 0.41866824 | None | None | N |
| M/S | 0.9674 | likely_pathogenic | 0.9558 | pathogenic | -2.664 | Highly Destabilizing | 0.728 | D | 0.739 | prob.delet. | None | None | None | None | N |
| M/T | 0.9168 | likely_pathogenic | 0.893 | pathogenic | -2.283 | Highly Destabilizing | 0.801 | D | 0.747 | deleterious | N | 0.475521385 | None | None | N |
| M/V | 0.312 | likely_benign | 0.3071 | benign | -1.526 | Destabilizing | 0.454 | N | 0.461 | neutral | N | 0.453399208 | None | None | N |
| M/W | 0.9605 | likely_pathogenic | 0.9539 | pathogenic | -1.269 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| M/Y | 0.8979 | likely_pathogenic | 0.8787 | pathogenic | -1.287 | Destabilizing | 0.974 | D | 0.808 | 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.