Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31779 | 95560;95561;95562 | chr2:178545901;178545900;178545899 | chr2:179410628;179410627;179410626 |
| N2AB | 30138 | 90637;90638;90639 | chr2:178545901;178545900;178545899 | chr2:179410628;179410627;179410626 |
| N2A | 29211 | 87856;87857;87858 | chr2:178545901;178545900;178545899 | chr2:179410628;179410627;179410626 |
| N2B | 22714 | 68365;68366;68367 | chr2:178545901;178545900;178545899 | chr2:179410628;179410627;179410626 |
| Novex-1 | 22839 | 68740;68741;68742 | chr2:178545901;178545900;178545899 | chr2:179410628;179410627;179410626 |
| Novex-2 | 22906 | 68941;68942;68943 | chr2:178545901;178545900;178545899 | chr2:179410628;179410627;179410626 |
| 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 | rs1460359915  |
-2.535 | 0.001 | N | 0.54 | 0.118 | 0.626236102369 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.12E-05 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/T | rs1460359915 |
-2.535 | 0.001 | N | 0.54 | 0.118 | 0.626236102369 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs1460359915 |
-2.535 | 0.001 | N | 0.54 | 0.118 | 0.626236102369 | gnomAD-4.0.0 | 1.4872E-05 | None | None | None | None | N | None | 1.33461E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.6952E-05 | 0 | 4.80338E-05 |
| I/V | rs886039071 |
None | None | N | 0.211 | 0.071 | 0.363751660372 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs886039071 |
None | None | N | 0.211 | 0.071 | 0.363751660372 | gnomAD-4.0.0 | 6.57091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47003E-05 | 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 | 0.3382 | likely_benign | 0.3713 | ambiguous | -2.628 | Highly Destabilizing | 0.072 | N | 0.699 | prob.neutral | None | None | None | None | N |
| I/C | 0.5088 | ambiguous | 0.5185 | ambiguous | -1.626 | Destabilizing | 0.909 | D | 0.754 | deleterious | None | None | None | None | N |
| I/D | 0.8038 | likely_pathogenic | 0.8275 | pathogenic | -3.143 | Highly Destabilizing | 0.567 | D | 0.805 | deleterious | None | None | None | None | N |
| I/E | 0.6097 | likely_pathogenic | 0.6664 | pathogenic | -2.885 | Highly Destabilizing | 0.567 | D | 0.789 | deleterious | None | None | None | None | N |
| I/F | 0.2383 | likely_benign | 0.2514 | benign | -1.491 | Destabilizing | 0.567 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/G | 0.6644 | likely_pathogenic | 0.7062 | pathogenic | -3.15 | Highly Destabilizing | 0.567 | D | 0.778 | deleterious | None | None | None | None | N |
| I/H | 0.5053 | ambiguous | 0.53 | ambiguous | -2.724 | Highly Destabilizing | 0.968 | D | 0.816 | deleterious | None | None | None | None | N |
| I/K | 0.4308 | ambiguous | 0.464 | ambiguous | -1.867 | Destabilizing | 0.497 | N | 0.789 | deleterious | N | 0.495063224 | None | None | N |
| I/L | 0.1019 | likely_benign | 0.1051 | benign | -1.081 | Destabilizing | 0.025 | N | 0.441 | neutral | N | 0.467359335 | None | None | N |
| I/M | 0.1141 | likely_benign | 0.1206 | benign | -1.117 | Destabilizing | 0.497 | N | 0.727 | prob.delet. | N | 0.466177771 | None | None | N |
| I/N | 0.3399 | likely_benign | 0.3519 | ambiguous | -2.32 | Highly Destabilizing | 0.567 | D | 0.819 | deleterious | None | None | None | None | N |
| I/P | 0.9729 | likely_pathogenic | 0.9753 | pathogenic | -1.585 | Destabilizing | 0.726 | D | 0.812 | deleterious | None | None | None | None | N |
| I/Q | 0.392 | ambiguous | 0.435 | ambiguous | -2.105 | Highly Destabilizing | 0.726 | D | 0.835 | deleterious | None | None | None | None | N |
| I/R | 0.3454 | ambiguous | 0.3814 | ambiguous | -1.714 | Destabilizing | 0.497 | N | 0.827 | deleterious | N | 0.498642247 | None | None | N |
| I/S | 0.2879 | likely_benign | 0.3209 | benign | -2.884 | Highly Destabilizing | 0.157 | N | 0.734 | prob.delet. | None | None | None | None | N |
| I/T | 0.1934 | likely_benign | 0.2061 | benign | -2.499 | Highly Destabilizing | 0.001 | N | 0.54 | neutral | N | 0.479939056 | None | None | N |
| I/V | 0.068 | likely_benign | 0.0673 | benign | -1.585 | Destabilizing | None | N | 0.211 | neutral | N | 0.482846076 | None | None | N |
| I/W | 0.8346 | likely_pathogenic | 0.8457 | pathogenic | -1.941 | Destabilizing | 0.968 | D | 0.8 | deleterious | None | None | None | None | N |
| I/Y | 0.5306 | ambiguous | 0.5406 | ambiguous | -1.697 | Destabilizing | 0.726 | D | 0.779 | 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.