Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3196 | 9811;9812;9813 | chr2:178766498;178766497;178766496 | chr2:179631225;179631224;179631223 |
| N2AB | 3196 | 9811;9812;9813 | chr2:178766498;178766497;178766496 | chr2:179631225;179631224;179631223 |
| N2A | 3196 | 9811;9812;9813 | chr2:178766498;178766497;178766496 | chr2:179631225;179631224;179631223 |
| N2B | 3150 | 9673;9674;9675 | chr2:178766498;178766497;178766496 | chr2:179631225;179631224;179631223 |
| Novex-1 | 3150 | 9673;9674;9675 | chr2:178766498;178766497;178766496 | chr2:179631225;179631224;179631223 |
| Novex-2 | 3150 | 9673;9674;9675 | chr2:178766498;178766497;178766496 | chr2:179631225;179631224;179631223 |
| Novex-3 | 3196 | 9811;9812;9813 | chr2:178766498;178766497;178766496 | chr2:179631225;179631224;179631223 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1238502159  |
-1.158 | 1.0 | D | 0.873 | 0.676 | 0.643351887025 | gnomAD-2.1.1 | 7.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.55E-05 | 0 |
| Y/C | rs1238502159 |
-1.158 | 1.0 | D | 0.873 | 0.676 | 0.643351887025 | 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 |
| Y/C | rs1238502159 |
-1.158 | 1.0 | D | 0.873 | 0.676 | 0.643351887025 | gnomAD-4.0.0 | 3.0979E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23732E-06 | 0 | 0 |
| Y/F | None | None | 0.999 | N | 0.547 | 0.444 | 0.518092603711 | gnomAD-4.0.0 | 6.84084E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9931E-07 | 0 | 0 |
| Y/H | None | None | 1.0 | D | 0.75 | 0.579 | 0.50970329007 | gnomAD-4.0.0 | 1.20037E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31254E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9497 | likely_pathogenic | 0.947 | pathogenic | -2.042 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| Y/C | 0.8284 | likely_pathogenic | 0.8284 | pathogenic | -1.486 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.555064434 | None | None | N |
| Y/D | 0.9484 | likely_pathogenic | 0.9604 | pathogenic | -2.746 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | D | 0.55607731 | None | None | N |
| Y/E | 0.983 | likely_pathogenic | 0.9837 | pathogenic | -2.573 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| Y/F | 0.276 | likely_benign | 0.2817 | benign | -0.948 | Destabilizing | 0.999 | D | 0.547 | neutral | N | 0.507321551 | None | None | N |
| Y/G | 0.9344 | likely_pathogenic | 0.9367 | pathogenic | -2.369 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| Y/H | 0.9012 | likely_pathogenic | 0.9103 | pathogenic | -1.281 | Destabilizing | 1.0 | D | 0.75 | deleterious | D | 0.555064434 | None | None | N |
| Y/I | 0.8957 | likely_pathogenic | 0.8934 | pathogenic | -0.972 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| Y/K | 0.9855 | likely_pathogenic | 0.9861 | pathogenic | -1.886 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| Y/L | 0.7875 | likely_pathogenic | 0.7824 | pathogenic | -0.972 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| Y/M | 0.8811 | likely_pathogenic | 0.8906 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| Y/N | 0.8607 | likely_pathogenic | 0.8806 | pathogenic | -2.706 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.555064434 | None | None | N |
| Y/P | 0.9836 | likely_pathogenic | 0.9804 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| Y/Q | 0.9843 | likely_pathogenic | 0.9847 | pathogenic | -2.436 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| Y/R | 0.9757 | likely_pathogenic | 0.9754 | pathogenic | -1.875 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| Y/S | 0.9011 | likely_pathogenic | 0.9082 | pathogenic | -2.958 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | N | 0.503322992 | None | None | N |
| Y/T | 0.9422 | likely_pathogenic | 0.9408 | pathogenic | -2.67 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| Y/V | 0.8129 | likely_pathogenic | 0.8014 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| Y/W | 0.841 | likely_pathogenic | 0.8406 | pathogenic | -0.498 | Destabilizing | 1.0 | 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.