Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20601 | 62026;62027;62028 | chr2:178589924;178589923;178589922 | chr2:179454651;179454650;179454649 |
| N2AB | 18960 | 57103;57104;57105 | chr2:178589924;178589923;178589922 | chr2:179454651;179454650;179454649 |
| N2A | 18033 | 54322;54323;54324 | chr2:178589924;178589923;178589922 | chr2:179454651;179454650;179454649 |
| N2B | 11536 | 34831;34832;34833 | chr2:178589924;178589923;178589922 | chr2:179454651;179454650;179454649 |
| Novex-1 | 11661 | 35206;35207;35208 | chr2:178589924;178589923;178589922 | chr2:179454651;179454650;179454649 |
| Novex-2 | 11728 | 35407;35408;35409 | chr2:178589924;178589923;178589922 | chr2:179454651;179454650;179454649 |
| 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 | None | None | 0.993 | N | 0.429 | 0.377 | 0.621426341079 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/M | rs760014192  |
-0.96 | 1.0 | D | 0.809 | 0.487 | 0.570197126672 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.63E-05 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs760014192 |
-0.96 | 1.0 | D | 0.809 | 0.487 | 0.570197126672 | gnomAD-4.0.0 | 1.59243E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.78474E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9892 | likely_pathogenic | 0.991 | pathogenic | -2.279 | Highly Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| I/C | 0.991 | likely_pathogenic | 0.9915 | pathogenic | -1.426 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| I/D | 0.9985 | likely_pathogenic | 0.9988 | pathogenic | -2.196 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | I |
| I/E | 0.9955 | likely_pathogenic | 0.996 | pathogenic | -2.138 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | I |
| I/F | 0.9511 | likely_pathogenic | 0.9544 | pathogenic | -1.678 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | I |
| I/G | 0.9981 | likely_pathogenic | 0.9986 | pathogenic | -2.683 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | I |
| I/H | 0.9982 | likely_pathogenic | 0.9985 | pathogenic | -1.988 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| I/K | 0.9921 | likely_pathogenic | 0.9941 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.883 | deleterious | D | 0.545202426 | None | None | I |
| I/L | 0.6285 | likely_pathogenic | 0.6312 | pathogenic | -1.186 | Destabilizing | 0.993 | D | 0.429 | neutral | N | 0.492594274 | None | None | I |
| I/M | 0.622 | likely_pathogenic | 0.6222 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.532667579 | None | None | I |
| I/N | 0.9649 | likely_pathogenic | 0.9708 | pathogenic | -1.514 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | I |
| I/P | 0.9835 | likely_pathogenic | 0.9803 | pathogenic | -1.524 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | I |
| I/Q | 0.9952 | likely_pathogenic | 0.9959 | pathogenic | -1.655 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| I/R | 0.9927 | likely_pathogenic | 0.9939 | pathogenic | -1.013 | Destabilizing | 1.0 | D | 0.874 | deleterious | D | 0.545202426 | None | None | I |
| I/S | 0.9901 | likely_pathogenic | 0.9919 | pathogenic | -2.154 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | I |
| I/T | 0.9721 | likely_pathogenic | 0.9795 | pathogenic | -1.974 | Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.526337703 | None | None | I |
| I/V | 0.2091 | likely_benign | 0.2378 | benign | -1.524 | Destabilizing | 0.993 | D | 0.409 | neutral | N | 0.492087208 | None | None | I |
| I/W | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -1.871 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| I/Y | 0.9908 | likely_pathogenic | 0.9922 | pathogenic | -1.652 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | I |
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.