Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2674 | 8245;8246;8247 | chr2:178771307;178771306;178771305 | chr2:179636034;179636033;179636032 |
| N2AB | 2674 | 8245;8246;8247 | chr2:178771307;178771306;178771305 | chr2:179636034;179636033;179636032 |
| N2A | 2674 | 8245;8246;8247 | chr2:178771307;178771306;178771305 | chr2:179636034;179636033;179636032 |
| N2B | 2628 | 8107;8108;8109 | chr2:178771307;178771306;178771305 | chr2:179636034;179636033;179636032 |
| Novex-1 | 2628 | 8107;8108;8109 | chr2:178771307;178771306;178771305 | chr2:179636034;179636033;179636032 |
| Novex-2 | 2628 | 8107;8108;8109 | chr2:178771307;178771306;178771305 | chr2:179636034;179636033;179636032 |
| Novex-3 | 2674 | 8245;8246;8247 | chr2:178771307;178771306;178771305 | chr2:179636034;179636033;179636032 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/T | rs542196734  |
-2.281 | 1.0 | D | 0.753 | 0.468 | 0.714579403 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs542196734 |
-2.281 | 1.0 | D | 0.753 | 0.468 | 0.714579403 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs542196734 |
-2.281 | 1.0 | D | 0.753 | 0.468 | 0.714579403 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/T | rs542196734 |
-2.281 | 1.0 | D | 0.753 | 0.468 | 0.714579403 | gnomAD-4.0.0 | 6.5684E-06 | None | None | None | None | N | None | 0 | 6.5368E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.88 | likely_pathogenic | 0.8877 | pathogenic | -1.986 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| R/C | 0.3447 | ambiguous | 0.3543 | ambiguous | -2.249 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| R/D | 0.9698 | likely_pathogenic | 0.9668 | pathogenic | -1.334 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/E | 0.7341 | likely_pathogenic | 0.7327 | pathogenic | -1.136 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| R/F | 0.857 | likely_pathogenic | 0.8672 | pathogenic | -1.561 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| R/G | 0.8109 | likely_pathogenic | 0.8008 | pathogenic | -2.315 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.543085468 | None | None | N |
| R/H | 0.1633 | likely_benign | 0.174 | benign | -2.279 | Highly Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| R/I | 0.5872 | likely_pathogenic | 0.5995 | pathogenic | -1.045 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| R/K | 0.2566 | likely_benign | 0.2734 | benign | -1.69 | Destabilizing | 0.997 | D | 0.603 | neutral | D | 0.669556695 | None | None | N |
| R/L | 0.6164 | likely_pathogenic | 0.633 | pathogenic | -1.045 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| R/M | 0.6732 | likely_pathogenic | 0.6896 | pathogenic | -1.454 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.672967673 | None | None | N |
| R/N | 0.8874 | likely_pathogenic | 0.8876 | pathogenic | -1.695 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/P | 0.9941 | likely_pathogenic | 0.9916 | pathogenic | -1.346 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| R/Q | 0.1555 | likely_benign | 0.1644 | benign | -1.611 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/S | 0.8894 | likely_pathogenic | 0.8947 | pathogenic | -2.529 | Highly Destabilizing | 1.0 | D | 0.76 | deleterious | D | 0.543888861 | None | None | N |
| R/T | 0.7329 | likely_pathogenic | 0.7443 | pathogenic | -2.117 | Highly Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.574907084 | None | None | N |
| R/V | 0.6913 | likely_pathogenic | 0.7106 | pathogenic | -1.346 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| R/W | 0.3861 | ambiguous | 0.3789 | ambiguous | -1.142 | Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.635688702 | None | None | N |
| R/Y | 0.6171 | likely_pathogenic | 0.6303 | pathogenic | -0.913 | Destabilizing | 1.0 | D | 0.861 | 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.