Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25468 | 76627;76628;76629 | chr2:178569730;178569729;178569728 | chr2:179434457;179434456;179434455 |
| N2AB | 23827 | 71704;71705;71706 | chr2:178569730;178569729;178569728 | chr2:179434457;179434456;179434455 |
| N2A | 22900 | 68923;68924;68925 | chr2:178569730;178569729;178569728 | chr2:179434457;179434456;179434455 |
| N2B | 16403 | 49432;49433;49434 | chr2:178569730;178569729;178569728 | chr2:179434457;179434456;179434455 |
| Novex-1 | 16528 | 49807;49808;49809 | chr2:178569730;178569729;178569728 | chr2:179434457;179434456;179434455 |
| Novex-2 | 16595 | 50008;50009;50010 | chr2:178569730;178569729;178569728 | chr2:179434457;179434456;179434455 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.006 | N | 0.319 | 0.248 | 0.428169733428 | gnomAD-4.0.0 | 1.59256E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85936E-06 | 0 | 0 |
| V/L | rs200308639  |
-0.228 | 0.068 | N | 0.631 | 0.183 | 0.265929055128 | gnomAD-2.1.1 | 7.16E-05 | None | None | None | None | N | None | 7.44971E-04 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs200308639 |
-0.228 | 0.068 | N | 0.631 | 0.183 | 0.265929055128 | gnomAD-3.1.2 | 1.57832E-04 | None | None | None | None | N | None | 5.79402E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs200308639 |
-0.228 | 0.068 | N | 0.631 | 0.183 | 0.265929055128 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| V/L | rs200308639 |
-0.228 | 0.068 | N | 0.631 | 0.183 | 0.265929055128 | gnomAD-4.0.0 | 2.04562E-05 | None | None | None | None | N | None | 3.73313E-04 | 3.336E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.80446E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3174 | likely_benign | 0.3243 | benign | -1.935 | Destabilizing | 0.006 | N | 0.319 | neutral | N | 0.517505728 | None | None | N |
| V/C | 0.8277 | likely_pathogenic | 0.8469 | pathogenic | -1.433 | Destabilizing | 0.991 | D | 0.751 | deleterious | None | None | None | None | N |
| V/D | 0.9136 | likely_pathogenic | 0.9158 | pathogenic | -2.626 | Highly Destabilizing | 0.906 | D | 0.853 | deleterious | None | None | None | None | N |
| V/E | 0.8311 | likely_pathogenic | 0.8171 | pathogenic | -2.367 | Highly Destabilizing | 0.879 | D | 0.825 | deleterious | D | 0.528134902 | None | None | N |
| V/F | 0.2982 | likely_benign | 0.3305 | benign | -1.119 | Destabilizing | 0.826 | D | 0.777 | deleterious | None | None | None | None | N |
| V/G | 0.6743 | likely_pathogenic | 0.6657 | pathogenic | -2.509 | Highly Destabilizing | 0.338 | N | 0.787 | deleterious | D | 0.539655791 | None | None | N |
| V/H | 0.9353 | likely_pathogenic | 0.9371 | pathogenic | -2.325 | Highly Destabilizing | 0.991 | D | 0.848 | deleterious | None | None | None | None | N |
| V/I | 0.0695 | likely_benign | 0.0812 | benign | -0.321 | Destabilizing | 0.003 | N | 0.294 | neutral | N | 0.479829987 | None | None | N |
| V/K | 0.8978 | likely_pathogenic | 0.8913 | pathogenic | -1.678 | Destabilizing | 0.826 | D | 0.828 | deleterious | None | None | None | None | N |
| V/L | 0.2405 | likely_benign | 0.2805 | benign | -0.321 | Destabilizing | 0.068 | N | 0.631 | neutral | N | 0.464074176 | None | None | N |
| V/M | 0.1992 | likely_benign | 0.2096 | benign | -0.382 | Destabilizing | 0.826 | D | 0.688 | prob.neutral | None | None | None | None | N |
| V/N | 0.8294 | likely_pathogenic | 0.8628 | pathogenic | -2.103 | Highly Destabilizing | 0.967 | D | 0.848 | deleterious | None | None | None | None | N |
| V/P | 0.925 | likely_pathogenic | 0.9308 | pathogenic | -0.832 | Destabilizing | 0.906 | D | 0.825 | deleterious | None | None | None | None | N |
| V/Q | 0.8606 | likely_pathogenic | 0.8533 | pathogenic | -1.875 | Destabilizing | 0.967 | D | 0.819 | deleterious | None | None | None | None | N |
| V/R | 0.8768 | likely_pathogenic | 0.8734 | pathogenic | -1.629 | Destabilizing | 0.906 | D | 0.853 | deleterious | None | None | None | None | N |
| V/S | 0.6695 | likely_pathogenic | 0.6974 | pathogenic | -2.71 | Highly Destabilizing | 0.404 | N | 0.769 | deleterious | None | None | None | None | N |
| V/T | 0.4161 | ambiguous | 0.4386 | ambiguous | -2.293 | Highly Destabilizing | 0.575 | D | 0.656 | neutral | None | None | None | None | N |
| V/W | 0.9251 | likely_pathogenic | 0.9239 | pathogenic | -1.682 | Destabilizing | 0.991 | D | 0.817 | deleterious | None | None | None | None | N |
| V/Y | 0.7854 | likely_pathogenic | 0.8077 | pathogenic | -1.239 | Destabilizing | 0.906 | D | 0.755 | 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.