Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26362 | 79309;79310;79311 | chr2:178567048;178567047;178567046 | chr2:179431775;179431774;179431773 |
| N2AB | 24721 | 74386;74387;74388 | chr2:178567048;178567047;178567046 | chr2:179431775;179431774;179431773 |
| N2A | 23794 | 71605;71606;71607 | chr2:178567048;178567047;178567046 | chr2:179431775;179431774;179431773 |
| N2B | 17297 | 52114;52115;52116 | chr2:178567048;178567047;178567046 | chr2:179431775;179431774;179431773 |
| Novex-1 | 17422 | 52489;52490;52491 | chr2:178567048;178567047;178567046 | chr2:179431775;179431774;179431773 |
| Novex-2 | 17489 | 52690;52691;52692 | chr2:178567048;178567047;178567046 | chr2:179431775;179431774;179431773 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs529839486  |
-2.226 | 0.684 | N | 0.737 | 0.409 | None | gnomAD-2.1.1 | 2.28689E-04 | None | None | None | None | N | None | 4.13E-05 | 1.41387E-03 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-05 | 4.21704E-04 |
| M/T | rs529839486 |
-2.226 | 0.684 | N | 0.737 | 0.409 | None | gnomAD-3.1.2 | 2.82642E-04 | None | None | None | None | N | None | 1.20633E-04 | 1.7038E-03 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 3.82044E-03 |
| M/T | rs529839486 |
-2.226 | 0.684 | N | 0.737 | 0.409 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| M/T | rs529839486 |
-2.226 | 0.684 | N | 0.737 | 0.409 | None | gnomAD-4.0.0 | 1.59265E-04 | None | None | None | None | N | None | 9.3306E-05 | 1.46667E-03 | None | 3.37861E-05 | 0 | None | 1.56191E-05 | 1.65017E-04 | 1.09354E-04 | 0 | 4.80307E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3788 | ambiguous | 0.3837 | ambiguous | -2.49 | Highly Destabilizing | 0.543 | D | 0.727 | prob.delet. | None | None | None | None | N |
| M/C | 0.5519 | ambiguous | 0.5441 | ambiguous | -2.388 | Highly Destabilizing | 0.996 | D | 0.73 | prob.delet. | None | None | None | None | N |
| M/D | 0.9633 | likely_pathogenic | 0.9539 | pathogenic | -2.287 | Highly Destabilizing | 0.953 | D | 0.771 | deleterious | None | None | None | None | N |
| M/E | 0.7793 | likely_pathogenic | 0.756 | pathogenic | -2.11 | Highly Destabilizing | 0.742 | D | 0.709 | prob.delet. | None | None | None | None | N |
| M/F | 0.508 | ambiguous | 0.4911 | ambiguous | -0.956 | Destabilizing | 0.984 | D | 0.78 | deleterious | None | None | None | None | N |
| M/G | 0.7002 | likely_pathogenic | 0.6823 | pathogenic | -2.906 | Highly Destabilizing | 0.742 | D | 0.737 | prob.delet. | None | None | None | None | N |
| M/H | 0.6015 | likely_pathogenic | 0.5867 | pathogenic | -2.367 | Highly Destabilizing | 0.953 | D | 0.722 | prob.delet. | None | None | None | None | N |
| M/I | 0.5353 | ambiguous | 0.5785 | pathogenic | -1.306 | Destabilizing | 0.815 | D | 0.751 | deleterious | N | 0.435073558 | None | None | N |
| M/K | 0.2732 | likely_benign | 0.2769 | benign | -1.757 | Destabilizing | 0.521 | D | 0.735 | prob.delet. | N | 0.457563629 | None | None | N |
| M/L | 0.1806 | likely_benign | 0.1717 | benign | -1.306 | Destabilizing | 0.281 | N | 0.503 | neutral | N | 0.447290707 | None | None | N |
| M/N | 0.6632 | likely_pathogenic | 0.6453 | pathogenic | -1.936 | Destabilizing | 0.91 | D | 0.749 | deleterious | None | None | None | None | N |
| M/P | 0.9938 | likely_pathogenic | 0.9929 | pathogenic | -1.683 | Destabilizing | 0.984 | D | 0.745 | deleterious | None | None | None | None | N |
| M/Q | 0.2976 | likely_benign | 0.2927 | benign | -1.756 | Destabilizing | 0.742 | D | 0.752 | deleterious | None | None | None | None | N |
| M/R | 0.2397 | likely_benign | 0.2338 | benign | -1.589 | Destabilizing | 0.007 | N | 0.496 | neutral | N | 0.386818252 | None | None | N |
| M/S | 0.3267 | likely_benign | 0.3254 | benign | -2.505 | Highly Destabilizing | 0.742 | D | 0.737 | prob.delet. | None | None | None | None | N |
| M/T | 0.1673 | likely_benign | 0.1707 | benign | -2.225 | Highly Destabilizing | 0.684 | D | 0.737 | prob.delet. | N | 0.447578709 | None | None | N |
| M/V | 0.1264 | likely_benign | 0.1453 | benign | -1.683 | Destabilizing | 0.645 | D | 0.755 | deleterious | N | 0.453677962 | None | None | N |
| M/W | 0.82 | likely_pathogenic | 0.7927 | pathogenic | -1.224 | Destabilizing | 0.996 | D | 0.729 | prob.delet. | None | None | None | None | N |
| M/Y | 0.7781 | likely_pathogenic | 0.7321 | pathogenic | -1.261 | Destabilizing | 0.984 | D | 0.777 | 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.