Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18339 | 55240;55241;55242 | chr2:178602387;178602386;178602385 | chr2:179467114;179467113;179467112 |
| N2AB | 16698 | 50317;50318;50319 | chr2:178602387;178602386;178602385 | chr2:179467114;179467113;179467112 |
| N2A | 15771 | 47536;47537;47538 | chr2:178602387;178602386;178602385 | chr2:179467114;179467113;179467112 |
| N2B | 9274 | 28045;28046;28047 | chr2:178602387;178602386;178602385 | chr2:179467114;179467113;179467112 |
| Novex-1 | 9399 | 28420;28421;28422 | chr2:178602387;178602386;178602385 | chr2:179467114;179467113;179467112 |
| Novex-2 | 9466 | 28621;28622;28623 | chr2:178602387;178602386;178602385 | chr2:179467114;179467113;179467112 |
| 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 | rs773396552  |
-1.483 | 1.0 | D | 0.84 | 0.676 | 0.841067931832 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 1.66113E-04 |
| L/M | rs773396552 |
-1.483 | 1.0 | D | 0.84 | 0.676 | 0.841067931832 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/M | rs773396552 |
-1.483 | 1.0 | D | 0.84 | 0.676 | 0.841067931832 | gnomAD-4.0.0 | 3.53441E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.83335E-05 | 0 | 0 |
| L/V | rs773396552 |
None | 0.999 | D | 0.834 | 0.717 | 0.778441100154 | gnomAD-4.0.0 | 6.84569E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65766E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9355 | likely_pathogenic | 0.9454 | pathogenic | -2.591 | Highly Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| L/C | 0.8925 | likely_pathogenic | 0.9177 | pathogenic | -2.081 | Highly Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| L/D | 0.9987 | likely_pathogenic | 0.9992 | pathogenic | -2.498 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| L/E | 0.9902 | likely_pathogenic | 0.9933 | pathogenic | -2.318 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/F | 0.8321 | likely_pathogenic | 0.8738 | pathogenic | -1.724 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/G | 0.9863 | likely_pathogenic | 0.9885 | pathogenic | -3.113 | Highly Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| L/H | 0.9834 | likely_pathogenic | 0.9874 | pathogenic | -2.43 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/I | 0.2499 | likely_benign | 0.2643 | benign | -1.108 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| L/K | 0.9816 | likely_pathogenic | 0.9836 | pathogenic | -1.901 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/M | 0.3998 | ambiguous | 0.4887 | ambiguous | -1.068 | Destabilizing | 1.0 | D | 0.84 | deleterious | D | 0.590915718 | None | None | N |
| L/N | 0.9896 | likely_pathogenic | 0.9933 | pathogenic | -2.115 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| L/P | 0.984 | likely_pathogenic | 0.9872 | pathogenic | -1.58 | Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.665551294 | None | None | N |
| L/Q | 0.9604 | likely_pathogenic | 0.9689 | pathogenic | -2.064 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.628172785 | None | None | N |
| L/R | 0.9626 | likely_pathogenic | 0.9655 | pathogenic | -1.509 | Destabilizing | 1.0 | D | 0.846 | deleterious | D | 0.665551294 | None | None | N |
| L/S | 0.9891 | likely_pathogenic | 0.9926 | pathogenic | -2.902 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/T | 0.9231 | likely_pathogenic | 0.9401 | pathogenic | -2.567 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/V | 0.279 | likely_benign | 0.2906 | benign | -1.58 | Destabilizing | 0.999 | D | 0.834 | deleterious | D | 0.579337846 | None | None | N |
| L/W | 0.9741 | likely_pathogenic | 0.983 | pathogenic | -1.981 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| L/Y | 0.982 | likely_pathogenic | 0.9864 | pathogenic | -1.726 | 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.