Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28812 | 86659;86660;86661 | chr2:178559698;178559697;178559696 | chr2:179424425;179424424;179424423 |
| N2AB | 27171 | 81736;81737;81738 | chr2:178559698;178559697;178559696 | chr2:179424425;179424424;179424423 |
| N2A | 26244 | 78955;78956;78957 | chr2:178559698;178559697;178559696 | chr2:179424425;179424424;179424423 |
| N2B | 19747 | 59464;59465;59466 | chr2:178559698;178559697;178559696 | chr2:179424425;179424424;179424423 |
| Novex-1 | 19872 | 59839;59840;59841 | chr2:178559698;178559697;178559696 | chr2:179424425;179424424;179424423 |
| Novex-2 | 19939 | 60040;60041;60042 | chr2:178559698;178559697;178559696 | chr2:179424425;179424424;179424423 |
| 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/T | rs727504959  |
-1.291 | 0.124 | D | 0.795 | 0.755 | 0.757070926547 | gnomAD-2.1.1 | 1.65E-05 | None | None | None | None | N | None | 0 | 2.93E-05 | None | 0 | 0 | None | 0 | None | 4.8E-05 | 1.82E-05 | 0 |
| I/T | rs727504959 |
-1.291 | 0.124 | D | 0.795 | 0.755 | 0.757070926547 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs727504959 |
-1.291 | 0.124 | D | 0.795 | 0.755 | 0.757070926547 | gnomAD-4.0.0 | 1.80386E-05 | None | None | None | None | N | None | 0 | 1.67785E-05 | None | 0 | 0 | None | 7.86015E-05 | 0 | 1.69967E-05 | 0 | 4.82191E-05 |
| I/V | rs201918596 |
-0.993 | 0.001 | D | 0.357 | 0.229 | None | gnomAD-2.1.1 | 2.37328E-04 | None | None | None | None | N | None | 2.60999E-03 | 2.86E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.44051E-04 |
| I/V | rs201918596 |
-0.993 | 0.001 | D | 0.357 | 0.229 | None | gnomAD-3.1.2 | 6.899E-04 | None | None | None | None | N | None | 2.48492E-03 | 1.30941E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs201918596 |
-0.993 | 0.001 | D | 0.357 | 0.229 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 3.8E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs201918596 |
-0.993 | 0.001 | D | 0.357 | 0.229 | None | gnomAD-4.0.0 | 1.27505E-04 | None | None | None | None | N | None | 2.62996E-03 | 5.03389E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 8.03626E-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 | 0.6433 | likely_pathogenic | 0.5902 | pathogenic | -2.564 | Highly Destabilizing | 0.157 | N | 0.742 | deleterious | None | None | None | None | N |
| I/C | 0.8963 | likely_pathogenic | 0.8713 | pathogenic | -2.299 | Highly Destabilizing | 0.909 | D | 0.775 | deleterious | None | None | None | None | N |
| I/D | 0.9946 | likely_pathogenic | 0.9921 | pathogenic | -2.816 | Highly Destabilizing | 0.726 | D | 0.872 | deleterious | None | None | None | None | N |
| I/E | 0.979 | likely_pathogenic | 0.9728 | pathogenic | -2.633 | Highly Destabilizing | 0.726 | D | 0.87 | deleterious | None | None | None | None | N |
| I/F | 0.4824 | ambiguous | 0.4307 | ambiguous | -1.649 | Destabilizing | 0.497 | N | 0.719 | prob.delet. | D | 0.620547096 | None | None | N |
| I/G | 0.9695 | likely_pathogenic | 0.956 | pathogenic | -3.079 | Highly Destabilizing | 0.726 | D | 0.861 | deleterious | None | None | None | None | N |
| I/H | 0.974 | likely_pathogenic | 0.965 | pathogenic | -2.427 | Highly Destabilizing | 0.968 | D | 0.857 | deleterious | None | None | None | None | N |
| I/K | 0.961 | likely_pathogenic | 0.9512 | pathogenic | -1.928 | Destabilizing | 0.726 | D | 0.869 | deleterious | None | None | None | None | N |
| I/L | 0.2109 | likely_benign | 0.1743 | benign | -1.095 | Destabilizing | None | N | 0.342 | neutral | D | 0.54836229 | None | None | N |
| I/M | 0.1794 | likely_benign | 0.1631 | benign | -1.241 | Destabilizing | 0.497 | N | 0.707 | prob.neutral | D | 0.594605376 | None | None | N |
| I/N | 0.9446 | likely_pathogenic | 0.9251 | pathogenic | -2.209 | Highly Destabilizing | 0.859 | D | 0.861 | deleterious | D | 0.621556118 | None | None | N |
| I/P | 0.9897 | likely_pathogenic | 0.985 | pathogenic | -1.563 | Destabilizing | 0.89 | D | 0.869 | deleterious | None | None | None | None | N |
| I/Q | 0.9598 | likely_pathogenic | 0.9484 | pathogenic | -2.159 | Highly Destabilizing | 0.89 | D | 0.871 | deleterious | None | None | None | None | N |
| I/R | 0.936 | likely_pathogenic | 0.9246 | pathogenic | -1.559 | Destabilizing | 0.726 | D | 0.865 | deleterious | None | None | None | None | N |
| I/S | 0.8437 | likely_pathogenic | 0.8124 | pathogenic | -2.95 | Highly Destabilizing | 0.497 | N | 0.84 | deleterious | D | 0.605536757 | None | None | N |
| I/T | 0.4998 | ambiguous | 0.4411 | ambiguous | -2.618 | Highly Destabilizing | 0.124 | N | 0.795 | deleterious | D | 0.605133148 | None | None | N |
| I/V | 0.0609 | likely_benign | 0.0605 | benign | -1.563 | Destabilizing | 0.001 | N | 0.357 | neutral | D | 0.543561975 | None | None | N |
| I/W | 0.9728 | likely_pathogenic | 0.9682 | pathogenic | -1.933 | Destabilizing | 0.968 | D | 0.852 | deleterious | None | None | None | None | N |
| I/Y | 0.9337 | likely_pathogenic | 0.9166 | pathogenic | -1.674 | Destabilizing | 0.726 | D | 0.787 | 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.