Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6099 | 18520;18521;18522 | chr2:178730105;178730104;178730103 | chr2:179594832;179594831;179594830 |
| N2AB | 5782 | 17569;17570;17571 | chr2:178730105;178730104;178730103 | chr2:179594832;179594831;179594830 |
| N2A | 4855 | 14788;14789;14790 | chr2:178730105;178730104;178730103 | chr2:179594832;179594831;179594830 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs370109572  |
-1.502 | 0.497 | N | 0.739 | 0.247 | None | gnomAD-2.1.1 | 5.39E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.02338E-04 | 1.41363E-04 |
| L/F | rs370109572 |
-1.502 | 0.497 | N | 0.739 | 0.247 | None | gnomAD-3.1.2 | 6.68E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.4824E-04 | 0 | 0 |
| L/F | rs370109572 |
-1.502 | 0.497 | N | 0.739 | 0.247 | None | gnomAD-4.0.0 | 8.05698E-05 | None | None | None | None | N | None | 2.71312E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.05627E-04 | 0 | 4.92951E-05 |
| L/V | rs370109572 |
-1.121 | 0.001 | N | 0.359 | 0.099 | 0.282179105231 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs370109572 |
-1.121 | 0.001 | N | 0.359 | 0.099 | 0.282179105231 | gnomAD-3.1.2 | 6.68E-06 | None | None | None | None | N | None | 0 | 6.65E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs370109572 |
-1.121 | 0.001 | N | 0.359 | 0.099 | 0.282179105231 | gnomAD-4.0.0 | 1.88836E-06 | None | None | None | None | N | None | 0 | 3.40055E-05 | None | 0 | 0 | None | 0 | 0 | 8.58758E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8054 | likely_pathogenic | 0.8037 | pathogenic | -2.862 | Highly Destabilizing | 0.157 | N | 0.7 | prob.neutral | None | None | None | None | N |
| L/C | 0.8173 | likely_pathogenic | 0.8035 | pathogenic | -2.54 | Highly Destabilizing | 0.909 | D | 0.757 | deleterious | None | None | None | None | N |
| L/D | 0.9951 | likely_pathogenic | 0.9957 | pathogenic | -3.146 | Highly Destabilizing | 0.726 | D | 0.861 | deleterious | None | None | None | None | N |
| L/E | 0.9781 | likely_pathogenic | 0.9809 | pathogenic | -2.939 | Highly Destabilizing | 0.726 | D | 0.861 | deleterious | None | None | None | None | N |
| L/F | 0.4053 | ambiguous | 0.4328 | ambiguous | -1.836 | Destabilizing | 0.497 | N | 0.739 | prob.delet. | N | 0.51766765 | None | None | N |
| L/G | 0.9651 | likely_pathogenic | 0.9664 | pathogenic | -3.4 | Highly Destabilizing | 0.726 | D | 0.86 | deleterious | None | None | None | None | N |
| L/H | 0.9325 | likely_pathogenic | 0.9358 | pathogenic | -2.717 | Highly Destabilizing | 0.958 | D | 0.837 | deleterious | D | 0.545268559 | None | None | N |
| L/I | 0.0657 | likely_benign | 0.0721 | benign | -1.305 | Destabilizing | 0.001 | N | 0.36 | neutral | N | 0.493140933 | None | None | N |
| L/K | 0.9683 | likely_pathogenic | 0.9739 | pathogenic | -2.256 | Highly Destabilizing | 0.726 | D | 0.844 | deleterious | None | None | None | None | N |
| L/M | 0.2685 | likely_benign | 0.2736 | benign | -1.391 | Destabilizing | 0.567 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/N | 0.9617 | likely_pathogenic | 0.9695 | pathogenic | -2.598 | Highly Destabilizing | 0.89 | D | 0.845 | deleterious | None | None | None | None | N |
| L/P | 0.9712 | likely_pathogenic | 0.976 | pathogenic | -1.805 | Destabilizing | 0.002 | N | 0.677 | prob.neutral | D | 0.545268559 | None | None | N |
| L/Q | 0.9254 | likely_pathogenic | 0.9282 | pathogenic | -2.508 | Highly Destabilizing | 0.89 | D | 0.826 | deleterious | None | None | None | None | N |
| L/R | 0.9291 | likely_pathogenic | 0.9334 | pathogenic | -1.86 | Destabilizing | 0.667 | D | 0.819 | deleterious | D | 0.545268559 | None | None | N |
| L/S | 0.9374 | likely_pathogenic | 0.9414 | pathogenic | -3.355 | Highly Destabilizing | 0.567 | D | 0.834 | deleterious | None | None | None | None | N |
| L/T | 0.7976 | likely_pathogenic | 0.8056 | pathogenic | -2.997 | Highly Destabilizing | 0.272 | N | 0.798 | deleterious | None | None | None | None | N |
| L/V | 0.0736 | likely_benign | 0.0747 | benign | -1.805 | Destabilizing | 0.001 | N | 0.359 | neutral | N | 0.502456131 | None | None | N |
| L/W | 0.8718 | likely_pathogenic | 0.8774 | pathogenic | -2.141 | Highly Destabilizing | 0.968 | D | 0.813 | deleterious | None | None | None | None | N |
| L/Y | 0.8658 | likely_pathogenic | 0.8774 | pathogenic | -1.926 | Destabilizing | 0.726 | D | 0.759 | 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.