Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20102 | 60529;60530;60531 | chr2:178591421;178591420;178591419 | chr2:179456148;179456147;179456146 |
| N2AB | 18461 | 55606;55607;55608 | chr2:178591421;178591420;178591419 | chr2:179456148;179456147;179456146 |
| N2A | 17534 | 52825;52826;52827 | chr2:178591421;178591420;178591419 | chr2:179456148;179456147;179456146 |
| N2B | 11037 | 33334;33335;33336 | chr2:178591421;178591420;178591419 | chr2:179456148;179456147;179456146 |
| Novex-1 | 11162 | 33709;33710;33711 | chr2:178591421;178591420;178591419 | chr2:179456148;179456147;179456146 |
| Novex-2 | 11229 | 33910;33911;33912 | chr2:178591421;178591420;178591419 | chr2:179456148;179456147;179456146 |
| 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/L | rs755647048  |
-0.428 | 0.007 | D | 0.277 | 0.208 | 0.539792608675 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.05E-06 | 0 |
| I/L | rs755647048 |
-0.428 | 0.007 | D | 0.277 | 0.208 | 0.539792608675 | gnomAD-4.0.0 | 6.86685E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01326E-07 | 0 | 0 |
| I/M | None | None | 0.001 | N | 0.225 | 0.109 | 0.421184727016 | gnomAD-4.0.0 | 1.60376E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.7767E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs998020901 |
-1.961 | 0.183 | D | 0.616 | 0.443 | 0.703810458386 | gnomAD-2.1.1 | 4.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.05E-06 | 0 |
| I/T | rs998020901 |
-1.961 | 0.183 | D | 0.616 | 0.443 | 0.703810458386 | gnomAD-4.0.0 | 1.60437E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87704E-06 | 0 | 0 |
| I/V | rs755647048 |
-0.931 | 0.001 | N | 0.194 | 0.119 | 0.494433119893 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.05E-06 | 0 |
| I/V | rs755647048 |
-0.931 | 0.001 | N | 0.194 | 0.119 | 0.494433119893 | gnomAD-4.0.0 | 5.49348E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.30928E-06 | 0 | 1.66262E-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 | 0.8492 | likely_pathogenic | 0.8932 | pathogenic | -1.682 | Destabilizing | 0.129 | N | 0.526 | neutral | None | None | None | None | N |
| I/C | 0.8684 | likely_pathogenic | 0.9027 | pathogenic | -1.076 | Destabilizing | 0.94 | D | 0.732 | prob.delet. | None | None | None | None | N |
| I/D | 0.9949 | likely_pathogenic | 0.9969 | pathogenic | -0.809 | Destabilizing | 0.94 | D | 0.791 | deleterious | None | None | None | None | N |
| I/E | 0.9754 | likely_pathogenic | 0.9856 | pathogenic | -0.755 | Destabilizing | 0.593 | D | 0.754 | deleterious | None | None | None | None | N |
| I/F | 0.2152 | likely_benign | 0.2772 | benign | -1.05 | Destabilizing | 0.418 | N | 0.615 | neutral | None | None | None | None | N |
| I/G | 0.9688 | likely_pathogenic | 0.9792 | pathogenic | -2.057 | Highly Destabilizing | 0.593 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/H | 0.9233 | likely_pathogenic | 0.9509 | pathogenic | -1.313 | Destabilizing | 0.983 | D | 0.791 | deleterious | None | None | None | None | N |
| I/K | 0.9013 | likely_pathogenic | 0.9375 | pathogenic | -0.998 | Destabilizing | 0.351 | N | 0.728 | prob.delet. | D | 0.523910118 | None | None | N |
| I/L | 0.1336 | likely_benign | 0.1533 | benign | -0.705 | Destabilizing | 0.007 | N | 0.277 | neutral | D | 0.525077566 | None | None | N |
| I/M | 0.1091 | likely_benign | 0.1351 | benign | -0.639 | Destabilizing | 0.001 | N | 0.225 | neutral | N | 0.505646443 | None | None | N |
| I/N | 0.9123 | likely_pathogenic | 0.9402 | pathogenic | -0.871 | Destabilizing | 0.836 | D | 0.788 | deleterious | None | None | None | None | N |
| I/P | 0.9844 | likely_pathogenic | 0.9854 | pathogenic | -1.0 | Destabilizing | 0.94 | D | 0.791 | deleterious | None | None | None | None | N |
| I/Q | 0.8874 | likely_pathogenic | 0.9298 | pathogenic | -0.963 | Destabilizing | 0.836 | D | 0.791 | deleterious | None | None | None | None | N |
| I/R | 0.8643 | likely_pathogenic | 0.911 | pathogenic | -0.575 | Destabilizing | 0.655 | D | 0.793 | deleterious | N | 0.512553813 | None | None | N |
| I/S | 0.8557 | likely_pathogenic | 0.8956 | pathogenic | -1.605 | Destabilizing | 0.418 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/T | 0.7537 | likely_pathogenic | 0.8241 | pathogenic | -1.424 | Destabilizing | 0.183 | N | 0.616 | neutral | D | 0.525520283 | None | None | N |
| I/V | 0.1241 | likely_benign | 0.1416 | benign | -1.0 | Destabilizing | 0.001 | N | 0.194 | neutral | N | 0.417898881 | None | None | N |
| I/W | 0.9002 | likely_pathogenic | 0.9182 | pathogenic | -1.149 | Destabilizing | 0.983 | D | 0.78 | deleterious | None | None | None | None | N |
| I/Y | 0.7357 | likely_pathogenic | 0.7873 | pathogenic | -0.895 | Destabilizing | 0.836 | D | 0.745 | 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.