Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22838 | 68737;68738;68739 | chr2:178578003;178578002;178578001 | chr2:179442730;179442729;179442728 |
| N2AB | 21197 | 63814;63815;63816 | chr2:178578003;178578002;178578001 | chr2:179442730;179442729;179442728 |
| N2A | 20270 | 61033;61034;61035 | chr2:178578003;178578002;178578001 | chr2:179442730;179442729;179442728 |
| N2B | 13773 | 41542;41543;41544 | chr2:178578003;178578002;178578001 | chr2:179442730;179442729;179442728 |
| Novex-1 | 13898 | 41917;41918;41919 | chr2:178578003;178578002;178578001 | chr2:179442730;179442729;179442728 |
| Novex-2 | 13965 | 42118;42119;42120 | chr2:178578003;178578002;178578001 | chr2:179442730;179442729;179442728 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs2046828341  |
None | 0.999 | N | 0.593 | 0.248 | 0.3691244813 | 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 |
| A/S | rs2046828341 |
None | 0.999 | N | 0.593 | 0.248 | 0.3691244813 | gnomAD-4.0.0 | 6.57514E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47085E-05 | 0 | 0 |
| A/V | rs372075439 |
-0.544 | 0.999 | N | 0.673 | 0.277 | None | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | N | None | 3.72301E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs372075439 |
-0.544 | 0.999 | N | 0.673 | 0.277 | None | gnomAD-3.1.2 | 1.31511E-04 | None | None | None | None | N | None | 4.82695E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs372075439 |
-0.544 | 0.999 | N | 0.673 | 0.277 | None | gnomAD-4.0.0 | 1.92204E-05 | None | None | None | None | N | None | 3.8679E-04 | 1.66867E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60128E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5803 | likely_pathogenic | 0.5751 | pathogenic | -1.615 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| A/D | 0.9959 | likely_pathogenic | 0.9969 | pathogenic | -2.78 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| A/E | 0.9931 | likely_pathogenic | 0.9949 | pathogenic | -2.582 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.500180554 | None | None | N |
| A/F | 0.9539 | likely_pathogenic | 0.9597 | pathogenic | -0.885 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| A/G | 0.6058 | likely_pathogenic | 0.6403 | pathogenic | -1.938 | Destabilizing | 0.999 | D | 0.544 | neutral | N | 0.474189487 | None | None | N |
| A/H | 0.9946 | likely_pathogenic | 0.9952 | pathogenic | -2.084 | Highly Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| A/I | 0.7163 | likely_pathogenic | 0.7295 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| A/K | 0.9981 | likely_pathogenic | 0.9984 | pathogenic | -1.38 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/L | 0.6124 | likely_pathogenic | 0.6449 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| A/M | 0.7817 | likely_pathogenic | 0.7863 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| A/N | 0.9754 | likely_pathogenic | 0.977 | pathogenic | -1.739 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| A/P | 0.8599 | likely_pathogenic | 0.8828 | pathogenic | -0.694 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.501122405 | None | None | N |
| A/Q | 0.9857 | likely_pathogenic | 0.9873 | pathogenic | -1.559 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| A/R | 0.9909 | likely_pathogenic | 0.9929 | pathogenic | -1.424 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/S | 0.3617 | ambiguous | 0.3622 | ambiguous | -2.106 | Highly Destabilizing | 0.999 | D | 0.593 | neutral | N | 0.481822809 | None | None | N |
| A/T | 0.542 | ambiguous | 0.5414 | ambiguous | -1.797 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.48465423 | None | None | N |
| A/V | 0.4542 | ambiguous | 0.458 | ambiguous | -0.694 | Destabilizing | 0.999 | D | 0.673 | prob.neutral | N | 0.509435244 | None | None | N |
| A/W | 0.9977 | likely_pathogenic | 0.9982 | pathogenic | -1.544 | Destabilizing | 1.0 | D | 0.721 | deleterious | None | None | None | None | N |
| A/Y | 0.9883 | likely_pathogenic | 0.9907 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.806 | 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.