Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29997 | 90214;90215;90216 | chr2:178552911;178552910;178552909 | chr2:179417638;179417637;179417636 |
| N2AB | 28356 | 85291;85292;85293 | chr2:178552911;178552910;178552909 | chr2:179417638;179417637;179417636 |
| N2A | 27429 | 82510;82511;82512 | chr2:178552911;178552910;178552909 | chr2:179417638;179417637;179417636 |
| N2B | 20932 | 63019;63020;63021 | chr2:178552911;178552910;178552909 | chr2:179417638;179417637;179417636 |
| Novex-1 | 21057 | 63394;63395;63396 | chr2:178552911;178552910;178552909 | chr2:179417638;179417637;179417636 |
| Novex-2 | 21124 | 63595;63596;63597 | chr2:178552911;178552910;178552909 | chr2:179417638;179417637;179417636 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | rs369855092  |
-1.424 | 1.0 | D | 0.843 | 0.643 | None | gnomAD-2.1.1 | 1.41317E-03 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.13436E-02 | None | 0 | 8.9E-06 | 4.98173E-04 |
| L/M | rs369855092 |
-1.424 | 1.0 | D | 0.843 | 0.643 | None | gnomAD-3.1.2 | 4.27395E-04 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 1.30814E-02 | 0 |
| L/M | rs369855092 |
-1.424 | 1.0 | D | 0.843 | 0.643 | None | 1000 genomes | 2.79553E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1.43E-02 | None |
| L/M | rs369855092 |
-1.424 | 1.0 | D | 0.843 | 0.643 | None | gnomAD-4.0.0 | 7.22552E-04 | None | None | None | None | N | None | 1.3333E-05 | 1.66678E-05 | None | 0 | 0 | None | 0 | 4.94886E-04 | 3.39041E-06 | 1.21678E-02 | 7.84176E-04 |
| L/V | None | None | 0.999 | D | 0.837 | 0.656 | 0.777181567074 | gnomAD-4.0.0 | 6.84218E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99447E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8223 | likely_pathogenic | 0.8241 | pathogenic | -2.3 | Highly Destabilizing | 0.999 | D | 0.833 | deleterious | None | None | None | None | N |
| L/C | 0.8273 | likely_pathogenic | 0.8247 | pathogenic | -1.832 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| L/D | 0.9893 | likely_pathogenic | 0.9906 | pathogenic | -1.319 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/E | 0.9642 | likely_pathogenic | 0.9674 | pathogenic | -1.17 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| L/F | 0.4417 | ambiguous | 0.4365 | ambiguous | -1.465 | Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.677977462 | None | None | N |
| L/G | 0.9505 | likely_pathogenic | 0.9511 | pathogenic | -2.779 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/H | 0.9141 | likely_pathogenic | 0.9262 | pathogenic | -1.902 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| L/I | 0.1487 | likely_benign | 0.1364 | benign | -0.972 | Destabilizing | 0.999 | D | 0.83 | deleterious | None | None | None | None | N |
| L/K | 0.9504 | likely_pathogenic | 0.9542 | pathogenic | -1.532 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/M | 0.2481 | likely_benign | 0.2502 | benign | -0.982 | Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.63641999 | None | None | N |
| L/N | 0.9417 | likely_pathogenic | 0.9482 | pathogenic | -1.61 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/P | 0.9285 | likely_pathogenic | 0.9425 | pathogenic | -1.389 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/Q | 0.8763 | likely_pathogenic | 0.8919 | pathogenic | -1.564 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/R | 0.9223 | likely_pathogenic | 0.9267 | pathogenic | -1.162 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/S | 0.9322 | likely_pathogenic | 0.9374 | pathogenic | -2.497 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | D | 0.678784679 | None | None | N |
| L/T | 0.7764 | likely_pathogenic | 0.7818 | pathogenic | -2.188 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/V | 0.1948 | likely_benign | 0.1766 | benign | -1.389 | Destabilizing | 0.999 | D | 0.837 | deleterious | D | 0.608126262 | None | None | N |
| L/W | 0.8736 | likely_pathogenic | 0.8919 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.782 | deleterious | D | 0.678784679 | None | None | N |
| L/Y | 0.8905 | likely_pathogenic | 0.9002 | pathogenic | -1.329 | Destabilizing | 1.0 | D | 0.829 | 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.