Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16422 | 49489;49490;49491 | chr2:178614133;178614132;178614131 | chr2:179478860;179478859;179478858 |
| N2AB | 14781 | 44566;44567;44568 | chr2:178614133;178614132;178614131 | chr2:179478860;179478859;179478858 |
| N2A | 13854 | 41785;41786;41787 | chr2:178614133;178614132;178614131 | chr2:179478860;179478859;179478858 |
| N2B | 7357 | 22294;22295;22296 | chr2:178614133;178614132;178614131 | chr2:179478860;179478859;179478858 |
| Novex-1 | 7482 | 22669;22670;22671 | chr2:178614133;178614132;178614131 | chr2:179478860;179478859;179478858 |
| Novex-2 | 7549 | 22870;22871;22872 | chr2:178614133;178614132;178614131 | chr2:179478860;179478859;179478858 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | None | None | 0.741 | N | 0.773 | 0.297 | 0.771231716895 | gnomAD-4.0.0 | 6.84697E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99808E-07 | 0 | 0 |
| I/T | rs746167353  |
-2.743 | 0.117 | N | 0.722 | 0.175 | 0.633018970913 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/T | rs746167353 |
-2.743 | 0.117 | N | 0.722 | 0.175 | 0.633018970913 | gnomAD-4.0.0 | 1.78021E-05 | None | None | None | None | N | None | 1.49692E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61965E-05 | 0 | 4.97611E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3747 | ambiguous | 0.337 | benign | -2.541 | Highly Destabilizing | 0.035 | N | 0.675 | prob.neutral | None | None | None | None | N |
| I/C | 0.5523 | ambiguous | 0.5343 | ambiguous | -1.424 | Destabilizing | 0.935 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/D | 0.7777 | likely_pathogenic | 0.7389 | pathogenic | -3.141 | Highly Destabilizing | 0.791 | D | 0.757 | deleterious | None | None | None | None | N |
| I/E | 0.5696 | likely_pathogenic | 0.5374 | ambiguous | -2.857 | Highly Destabilizing | 0.555 | D | 0.753 | deleterious | None | None | None | None | N |
| I/F | 0.2119 | likely_benign | 0.1933 | benign | -1.48 | Destabilizing | 0.188 | N | 0.719 | prob.delet. | N | 0.47994667 | None | None | N |
| I/G | 0.7131 | likely_pathogenic | 0.6726 | pathogenic | -3.089 | Highly Destabilizing | 0.555 | D | 0.756 | deleterious | None | None | None | None | N |
| I/H | 0.5182 | ambiguous | 0.47 | ambiguous | -2.753 | Highly Destabilizing | 0.935 | D | 0.758 | deleterious | None | None | None | None | N |
| I/K | 0.5214 | ambiguous | 0.4702 | ambiguous | -1.78 | Destabilizing | 0.555 | D | 0.757 | deleterious | None | None | None | None | N |
| I/L | 0.1069 | likely_benign | 0.1057 | benign | -0.906 | Destabilizing | None | N | 0.247 | neutral | N | 0.443664963 | None | None | N |
| I/M | 0.1206 | likely_benign | 0.1165 | benign | -0.925 | Destabilizing | 0.188 | N | 0.697 | prob.neutral | N | 0.479462092 | None | None | N |
| I/N | 0.3256 | likely_benign | 0.2844 | benign | -2.343 | Highly Destabilizing | 0.741 | D | 0.773 | deleterious | N | 0.475563764 | None | None | N |
| I/P | 0.9747 | likely_pathogenic | 0.9715 | pathogenic | -1.441 | Destabilizing | 0.791 | D | 0.758 | deleterious | None | None | None | None | N |
| I/Q | 0.4508 | ambiguous | 0.4052 | ambiguous | -2.071 | Highly Destabilizing | 0.791 | D | 0.762 | deleterious | None | None | None | None | N |
| I/R | 0.4418 | ambiguous | 0.3868 | ambiguous | -1.742 | Destabilizing | 0.555 | D | 0.771 | deleterious | None | None | None | None | N |
| I/S | 0.2879 | likely_benign | 0.2495 | benign | -2.868 | Highly Destabilizing | 0.484 | N | 0.741 | deleterious | N | 0.457469959 | None | None | N |
| I/T | 0.1973 | likely_benign | 0.1778 | benign | -2.447 | Highly Destabilizing | 0.117 | N | 0.722 | prob.delet. | N | 0.454003037 | None | None | N |
| I/V | 0.0633 | likely_benign | 0.0663 | benign | -1.441 | Destabilizing | None | N | 0.205 | neutral | N | 0.44192969 | None | None | N |
| I/W | 0.829 | likely_pathogenic | 0.8046 | pathogenic | -1.936 | Destabilizing | 0.935 | D | 0.765 | deleterious | None | None | None | None | N |
| I/Y | 0.5278 | ambiguous | 0.4875 | ambiguous | -1.669 | Destabilizing | 0.555 | D | 0.737 | prob.delet. | 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.