Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15562 | 46909;46910;46911 | chr2:178619633;178619632;178619631 | chr2:179484360;179484359;179484358 |
| N2AB | 13921 | 41986;41987;41988 | chr2:178619633;178619632;178619631 | chr2:179484360;179484359;179484358 |
| N2A | 12994 | 39205;39206;39207 | chr2:178619633;178619632;178619631 | chr2:179484360;179484359;179484358 |
| N2B | 6497 | 19714;19715;19716 | chr2:178619633;178619632;178619631 | chr2:179484360;179484359;179484358 |
| Novex-1 | 6622 | 20089;20090;20091 | chr2:178619633;178619632;178619631 | chr2:179484360;179484359;179484358 |
| Novex-2 | 6689 | 20290;20291;20292 | chr2:178619633;178619632;178619631 | chr2:179484360;179484359;179484358 |
| 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 | rs755020461  |
-1.844 | 1.0 | D | 0.753 | 0.519 | 0.708043090069 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| L/F | rs755020461 |
-1.844 | 1.0 | D | 0.753 | 0.519 | 0.708043090069 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs755020461 |
-1.844 | 1.0 | D | 0.753 | 0.519 | 0.708043090069 | gnomAD-4.0.0 | 3.10251E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.24209E-06 | 0 | 0 |
| L/V | rs755020461 |
None | 0.999 | D | 0.58 | 0.452 | 0.627110788713 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/V | rs755020461 |
None | 0.999 | D | 0.58 | 0.452 | 0.627110788713 | gnomAD-4.0.0 | 8.68702E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18779E-05 | 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 | 0.9163 | likely_pathogenic | 0.9101 | pathogenic | -2.883 | Highly Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| L/C | 0.9242 | likely_pathogenic | 0.9338 | pathogenic | -2.007 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -3.606 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| L/E | 0.9962 | likely_pathogenic | 0.995 | pathogenic | -3.273 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| L/F | 0.8279 | likely_pathogenic | 0.808 | pathogenic | -1.753 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.638875471 | None | None | N |
| L/G | 0.9871 | likely_pathogenic | 0.985 | pathogenic | -3.505 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/H | 0.9939 | likely_pathogenic | 0.9931 | pathogenic | -3.207 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | D | 0.643544881 | None | None | N |
| L/I | 0.2179 | likely_benign | 0.2281 | benign | -1.0 | Destabilizing | 0.999 | D | 0.569 | neutral | D | 0.636926397 | None | None | N |
| L/K | 0.9928 | likely_pathogenic | 0.99 | pathogenic | -2.234 | Highly Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| L/M | 0.4035 | ambiguous | 0.3946 | ambiguous | -1.132 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/N | 0.9962 | likely_pathogenic | 0.9947 | pathogenic | -2.987 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| L/P | 0.9959 | likely_pathogenic | 0.995 | pathogenic | -1.62 | Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.643544881 | None | None | N |
| L/Q | 0.9876 | likely_pathogenic | 0.985 | pathogenic | -2.614 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| L/R | 0.9833 | likely_pathogenic | 0.9814 | pathogenic | -2.296 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.642716894 | None | None | N |
| L/S | 0.9939 | likely_pathogenic | 0.9932 | pathogenic | -3.534 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| L/T | 0.956 | likely_pathogenic | 0.9482 | pathogenic | -3.032 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/V | 0.246 | likely_benign | 0.2853 | benign | -1.62 | Destabilizing | 0.999 | D | 0.58 | neutral | D | 0.588174689 | None | None | N |
| L/W | 0.9793 | likely_pathogenic | 0.9774 | pathogenic | -2.169 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| L/Y | 0.9788 | likely_pathogenic | 0.9762 | pathogenic | -1.969 | Destabilizing | 1.0 | D | 0.813 | 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.