Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27281 | 82066;82067;82068 | chr2:178564291;178564290;178564289 | chr2:179429018;179429017;179429016 |
| N2AB | 25640 | 77143;77144;77145 | chr2:178564291;178564290;178564289 | chr2:179429018;179429017;179429016 |
| N2A | 24713 | 74362;74363;74364 | chr2:178564291;178564290;178564289 | chr2:179429018;179429017;179429016 |
| N2B | 18216 | 54871;54872;54873 | chr2:178564291;178564290;178564289 | chr2:179429018;179429017;179429016 |
| Novex-1 | 18341 | 55246;55247;55248 | chr2:178564291;178564290;178564289 | chr2:179429018;179429017;179429016 |
| Novex-2 | 18408 | 55447;55448;55449 | chr2:178564291;178564290;178564289 | chr2:179429018;179429017;179429016 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs769303800  |
-1.242 | 1.0 | N | 0.723 | 0.345 | 0.536942225882 | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.13E-05 | 1.65728E-04 |
| Y/C | rs769303800 |
-1.242 | 1.0 | N | 0.723 | 0.345 | 0.536942225882 | gnomAD-4.0.0 | 4.585E-05 | None | None | None | None | N | None | 0 | 2.23624E-05 | None | 0 | 0 | None | 0 | 0 | 5.48679E-05 | 0 | 8.28281E-05 |
| Y/H | rs1032656784 |
-1.939 | 0.998 | N | 0.702 | 0.433 | 0.445007932271 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| Y/H | rs1032656784 |
-1.939 | 0.998 | N | 0.702 | 0.433 | 0.445007932271 | gnomAD-4.0.0 | 3.18379E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85834E-06 | 1.43271E-05 | 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 | 0.8466 | likely_pathogenic | 0.8495 | pathogenic | -2.423 | Highly Destabilizing | 0.985 | D | 0.687 | prob.neutral | None | None | None | None | N |
| Y/C | 0.375 | ambiguous | 0.369 | ambiguous | -1.254 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.479408452 | None | None | N |
| Y/D | 0.7673 | likely_pathogenic | 0.7651 | pathogenic | -1.708 | Destabilizing | 0.998 | D | 0.77 | deleterious | N | 0.497348122 | None | None | N |
| Y/E | 0.9278 | likely_pathogenic | 0.9262 | pathogenic | -1.596 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | N |
| Y/F | 0.1237 | likely_benign | 0.1231 | benign | -0.981 | Destabilizing | 0.031 | N | 0.324 | neutral | N | 0.44518427 | None | None | N |
| Y/G | 0.7703 | likely_pathogenic | 0.7854 | pathogenic | -2.772 | Highly Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| Y/H | 0.5198 | ambiguous | 0.5386 | ambiguous | -1.332 | Destabilizing | 0.998 | D | 0.702 | prob.neutral | N | 0.497348122 | None | None | N |
| Y/I | 0.7047 | likely_pathogenic | 0.702 | pathogenic | -1.339 | Destabilizing | 0.97 | D | 0.712 | prob.delet. | None | None | None | None | N |
| Y/K | 0.9043 | likely_pathogenic | 0.9166 | pathogenic | -1.714 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | N |
| Y/L | 0.5858 | likely_pathogenic | 0.5833 | pathogenic | -1.339 | Destabilizing | 0.871 | D | 0.683 | prob.neutral | None | None | None | None | N |
| Y/M | 0.729 | likely_pathogenic | 0.7339 | pathogenic | -1.009 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | N |
| Y/N | 0.5169 | ambiguous | 0.5256 | ambiguous | -2.196 | Highly Destabilizing | 0.998 | D | 0.75 | deleterious | N | 0.497094633 | None | None | N |
| Y/P | 0.9718 | likely_pathogenic | 0.9711 | pathogenic | -1.7 | Destabilizing | 0.999 | D | 0.776 | deleterious | None | None | None | None | N |
| Y/Q | 0.8612 | likely_pathogenic | 0.8636 | pathogenic | -2.04 | Highly Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| Y/R | 0.8606 | likely_pathogenic | 0.8687 | pathogenic | -1.357 | Destabilizing | 0.999 | D | 0.748 | deleterious | None | None | None | None | N |
| Y/S | 0.7067 | likely_pathogenic | 0.7077 | pathogenic | -2.595 | Highly Destabilizing | 0.998 | D | 0.727 | prob.delet. | N | 0.478141004 | None | None | N |
| Y/T | 0.8396 | likely_pathogenic | 0.8404 | pathogenic | -2.38 | Highly Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| Y/V | 0.6314 | likely_pathogenic | 0.6262 | pathogenic | -1.7 | Destabilizing | 0.97 | D | 0.686 | prob.neutral | None | None | None | None | N |
| Y/W | 0.5883 | likely_pathogenic | 0.5926 | pathogenic | -0.607 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | 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.