Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19339 | 58240;58241;58242 | chr2:178594479;178594478;178594477 | chr2:179459206;179459205;179459204 |
| N2AB | 17698 | 53317;53318;53319 | chr2:178594479;178594478;178594477 | chr2:179459206;179459205;179459204 |
| N2A | 16771 | 50536;50537;50538 | chr2:178594479;178594478;178594477 | chr2:179459206;179459205;179459204 |
| N2B | 10274 | 31045;31046;31047 | chr2:178594479;178594478;178594477 | chr2:179459206;179459205;179459204 |
| Novex-1 | 10399 | 31420;31421;31422 | chr2:178594479;178594478;178594477 | chr2:179459206;179459205;179459204 |
| Novex-2 | 10466 | 31621;31622;31623 | chr2:178594479;178594478;178594477 | chr2:179459206;179459205;179459204 |
| 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/F | rs368025965  |
-1.576 | 0.993 | N | 0.72 | 0.25 | 0.456830177556 | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.47E-05 | 0 |
| L/F | rs368025965 |
-1.576 | 0.993 | N | 0.72 | 0.25 | 0.456830177556 | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17675E-04 | 0 | 0 |
| L/F | rs368025965 |
-1.576 | 0.993 | N | 0.72 | 0.25 | 0.456830177556 | gnomAD-4.0.0 | 1.11578E-04 | None | None | None | None | N | None | 1.33551E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46666E-04 | 0 | 9.60861E-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 | 0.7189 | likely_pathogenic | 0.5953 | pathogenic | -2.489 | Highly Destabilizing | 0.983 | D | 0.646 | neutral | None | None | None | None | N |
| L/C | 0.7019 | likely_pathogenic | 0.6335 | pathogenic | -1.798 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/D | 0.9492 | likely_pathogenic | 0.9025 | pathogenic | -2.334 | Highly Destabilizing | 0.999 | D | 0.885 | deleterious | None | None | None | None | N |
| L/E | 0.8352 | likely_pathogenic | 0.7337 | pathogenic | -2.087 | Highly Destabilizing | 0.998 | D | 0.873 | deleterious | None | None | None | None | N |
| L/F | 0.4124 | ambiguous | 0.2609 | benign | -1.441 | Destabilizing | 0.993 | D | 0.72 | prob.delet. | N | 0.483155507 | None | None | N |
| L/G | 0.9069 | likely_pathogenic | 0.8297 | pathogenic | -3.069 | Highly Destabilizing | 0.998 | D | 0.853 | deleterious | None | None | None | None | N |
| L/H | 0.6874 | likely_pathogenic | 0.5133 | ambiguous | -2.442 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| L/I | 0.1399 | likely_benign | 0.1062 | benign | -0.809 | Destabilizing | 0.966 | D | 0.511 | neutral | None | None | None | None | N |
| L/K | 0.7527 | likely_pathogenic | 0.6115 | pathogenic | -1.741 | Destabilizing | 0.995 | D | 0.794 | deleterious | None | None | None | None | N |
| L/M | 0.1902 | likely_benign | 0.1546 | benign | -0.819 | Destabilizing | 0.898 | D | 0.461 | neutral | N | 0.492852425 | None | None | N |
| L/N | 0.7677 | likely_pathogenic | 0.6692 | pathogenic | -2.08 | Highly Destabilizing | 0.998 | D | 0.883 | deleterious | None | None | None | None | N |
| L/P | 0.8116 | likely_pathogenic | 0.6809 | pathogenic | -1.35 | Destabilizing | 0.999 | D | 0.884 | deleterious | None | None | None | None | N |
| L/Q | 0.6052 | likely_pathogenic | 0.4521 | ambiguous | -1.896 | Destabilizing | 0.998 | D | 0.854 | deleterious | None | None | None | None | N |
| L/R | 0.724 | likely_pathogenic | 0.5608 | ambiguous | -1.565 | Destabilizing | 0.998 | D | 0.843 | deleterious | None | None | None | None | N |
| L/S | 0.8263 | likely_pathogenic | 0.6817 | pathogenic | -2.889 | Highly Destabilizing | 0.997 | D | 0.775 | deleterious | N | 0.463508166 | None | None | N |
| L/T | 0.6275 | likely_pathogenic | 0.5089 | ambiguous | -2.478 | Highly Destabilizing | 0.995 | D | 0.736 | prob.delet. | None | None | None | None | N |
| L/V | 0.1639 | likely_benign | 0.1276 | benign | -1.35 | Destabilizing | 0.955 | D | 0.529 | neutral | N | 0.383722018 | None | None | N |
| L/W | 0.7904 | likely_pathogenic | 0.6148 | pathogenic | -1.748 | Destabilizing | 1.0 | D | 0.843 | deleterious | N | 0.489295229 | None | None | N |
| L/Y | 0.7432 | likely_pathogenic | 0.5887 | pathogenic | -1.471 | Destabilizing | 0.998 | D | 0.837 | 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.