Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19418 | 58477;58478;58479 | chr2:178594141;178594140;178594139 | chr2:179458868;179458867;179458866 |
| N2AB | 17777 | 53554;53555;53556 | chr2:178594141;178594140;178594139 | chr2:179458868;179458867;179458866 |
| N2A | 16850 | 50773;50774;50775 | chr2:178594141;178594140;178594139 | chr2:179458868;179458867;179458866 |
| N2B | 10353 | 31282;31283;31284 | chr2:178594141;178594140;178594139 | chr2:179458868;179458867;179458866 |
| Novex-1 | 10478 | 31657;31658;31659 | chr2:178594141;178594140;178594139 | chr2:179458868;179458867;179458866 |
| Novex-2 | 10545 | 31858;31859;31860 | chr2:178594141;178594140;178594139 | chr2:179458868;179458867;179458866 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1236311809  |
None | 0.22 | D | 0.648 | 0.53 | 0.610564787575 | gnomAD-4.0.0 | 4.77625E-06 | None | None | None | None | I | None | 1.69722E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | rs1236311809 |
-2.228 | 0.667 | D | 0.855 | 0.624 | 0.799865847574 | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | I | None | 2.29568E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/G | rs1236311809 |
-2.228 | 0.667 | D | 0.855 | 0.624 | 0.799865847574 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | rs1236311809 |
-2.228 | 0.667 | D | 0.855 | 0.624 | 0.799865847574 | gnomAD-4.0.0 | 3.84536E-06 | None | None | None | None | I | None | 5.07511E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs2050889894 |
None | None | N | 0.189 | 0.167 | 0.251639045875 | gnomAD-4.0.0 | 6.84362E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9957E-07 | 0 | 0 |
| V/L | None | None | 0.001 | D | 0.325 | 0.199 | 0.384419519794 | gnomAD-4.0.0 | 6.84362E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9957E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.385 | ambiguous | 0.4429 | ambiguous | -1.731 | Destabilizing | 0.22 | N | 0.648 | neutral | D | 0.572057716 | None | None | I |
| V/C | 0.806 | likely_pathogenic | 0.838 | pathogenic | -1.148 | Destabilizing | 0.968 | D | 0.701 | prob.neutral | None | None | None | None | I |
| V/D | 0.9366 | likely_pathogenic | 0.9585 | pathogenic | -2.116 | Highly Destabilizing | 0.667 | D | 0.854 | deleterious | D | 0.579273585 | None | None | I |
| V/E | 0.8681 | likely_pathogenic | 0.9105 | pathogenic | -1.929 | Destabilizing | 0.726 | D | 0.849 | deleterious | None | None | None | None | I |
| V/F | 0.422 | ambiguous | 0.4828 | ambiguous | -1.036 | Destabilizing | 0.497 | N | 0.742 | deleterious | D | 0.568572477 | None | None | I |
| V/G | 0.6191 | likely_pathogenic | 0.6105 | pathogenic | -2.228 | Highly Destabilizing | 0.667 | D | 0.855 | deleterious | D | 0.579273585 | None | None | I |
| V/H | 0.9467 | likely_pathogenic | 0.9625 | pathogenic | -1.921 | Destabilizing | 0.968 | D | 0.855 | deleterious | None | None | None | None | I |
| V/I | 0.0796 | likely_benign | 0.0838 | benign | -0.373 | Destabilizing | None | N | 0.189 | neutral | N | 0.415510015 | None | None | I |
| V/K | 0.904 | likely_pathogenic | 0.9322 | pathogenic | -1.463 | Destabilizing | 0.726 | D | 0.85 | deleterious | None | None | None | None | I |
| V/L | 0.3353 | likely_benign | 0.4136 | ambiguous | -0.373 | Destabilizing | 0.001 | N | 0.325 | neutral | D | 0.531610188 | None | None | I |
| V/M | 0.3052 | likely_benign | 0.3832 | ambiguous | -0.332 | Destabilizing | 0.567 | D | 0.638 | neutral | None | None | None | None | I |
| V/N | 0.8501 | likely_pathogenic | 0.8971 | pathogenic | -1.664 | Destabilizing | 0.89 | D | 0.857 | deleterious | None | None | None | None | I |
| V/P | 0.8637 | likely_pathogenic | 0.8801 | pathogenic | -0.796 | Destabilizing | 0.89 | D | 0.845 | deleterious | None | None | None | None | I |
| V/Q | 0.8688 | likely_pathogenic | 0.9079 | pathogenic | -1.559 | Destabilizing | 0.89 | D | 0.856 | deleterious | None | None | None | None | I |
| V/R | 0.88 | likely_pathogenic | 0.9107 | pathogenic | -1.274 | Destabilizing | 0.726 | D | 0.854 | deleterious | None | None | None | None | I |
| V/S | 0.6653 | likely_pathogenic | 0.7299 | pathogenic | -2.256 | Highly Destabilizing | 0.726 | D | 0.835 | deleterious | None | None | None | None | I |
| V/T | 0.495 | ambiguous | 0.5536 | ambiguous | -1.926 | Destabilizing | 0.272 | N | 0.685 | prob.neutral | None | None | None | None | I |
| V/W | 0.9513 | likely_pathogenic | 0.9636 | pathogenic | -1.506 | Destabilizing | 0.968 | D | 0.852 | deleterious | None | None | None | None | I |
| V/Y | 0.8356 | likely_pathogenic | 0.8764 | pathogenic | -1.082 | Destabilizing | 0.726 | D | 0.714 | prob.delet. | None | None | None | None | I |
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.