Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30639 | 92140;92141;92142 | chr2:178549807;178549806;178549805 | chr2:179414534;179414533;179414532 |
| N2AB | 28998 | 87217;87218;87219 | chr2:178549807;178549806;178549805 | chr2:179414534;179414533;179414532 |
| N2A | 28071 | 84436;84437;84438 | chr2:178549807;178549806;178549805 | chr2:179414534;179414533;179414532 |
| N2B | 21574 | 64945;64946;64947 | chr2:178549807;178549806;178549805 | chr2:179414534;179414533;179414532 |
| Novex-1 | 21699 | 65320;65321;65322 | chr2:178549807;178549806;178549805 | chr2:179414534;179414533;179414532 |
| Novex-2 | 21766 | 65521;65522;65523 | chr2:178549807;178549806;178549805 | chr2:179414534;179414533;179414532 |
| 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/P | None | None | 1.0 | D | 0.932 | 0.756 | 0.898461317554 |
Yu (2019) 
| None |
Other 
|
comp het with N19955I (in trans), c.44282-2A>G (in cis) | None | None | N | Genetic analysis of single patient with congenital titinopathy; comp het with N19955I; significant decrease in full-length titin protein in biopsy samples compared to WT | None | None | None | None | None | None | None | None | None | None | None |
| L/P | None | None | 1.0 | D | 0.932 | 0.756 | 0.898461317554 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| L/V | rs373049260 |
-1.387 | 0.767 | N | 0.345 | 0.186 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| L/V | rs373049260 |
-1.387 | 0.767 | N | 0.345 | 0.186 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/V | rs373049260 |
-1.387 | 0.767 | N | 0.345 | 0.186 | None | gnomAD-4.0.0 | 3.10959E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.2542E-06 | 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 | 0.9026 | likely_pathogenic | 0.8927 | pathogenic | -2.338 | Highly Destabilizing | 0.997 | D | 0.733 | prob.delet. | None | None | None | None | N |
| L/C | 0.8308 | likely_pathogenic | 0.7939 | pathogenic | -1.1 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.823 | Highly Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | None | N |
| L/E | 0.997 | likely_pathogenic | 0.9971 | pathogenic | -2.503 | Highly Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | None | N |
| L/F | 0.4017 | ambiguous | 0.4889 | ambiguous | -1.346 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/G | 0.9878 | likely_pathogenic | 0.9879 | pathogenic | -2.91 | Highly Destabilizing | 1.0 | D | 0.92 | deleterious | None | None | None | None | N |
| L/H | 0.9881 | likely_pathogenic | 0.9905 | pathogenic | -2.819 | Highly Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| L/I | 0.1032 | likely_benign | 0.1055 | benign | -0.598 | Destabilizing | 0.985 | D | 0.584 | neutral | None | None | None | None | N |
| L/K | 0.9951 | likely_pathogenic | 0.9956 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| L/M | 0.2365 | likely_benign | 0.2388 | benign | -0.818 | Destabilizing | 0.999 | D | 0.71 | prob.delet. | D | 0.530940194 | None | None | N |
| L/N | 0.9964 | likely_pathogenic | 0.9966 | pathogenic | -2.238 | Highly Destabilizing | 1.0 | D | 0.941 | deleterious | None | None | None | None | N |
| L/P | 0.9945 | likely_pathogenic | 0.9957 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.932 | deleterious | D | 0.563794569 | None | None | N |
| L/Q | 0.9859 | likely_pathogenic | 0.9873 | pathogenic | -1.791 | Destabilizing | 1.0 | D | 0.941 | deleterious | D | 0.563794569 | None | None | N |
| L/R | 0.9871 | likely_pathogenic | 0.9895 | pathogenic | -1.866 | Destabilizing | 1.0 | D | 0.932 | deleterious | D | 0.563794569 | None | None | N |
| L/S | 0.9875 | likely_pathogenic | 0.9882 | pathogenic | -2.604 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/T | 0.9551 | likely_pathogenic | 0.951 | pathogenic | -2.122 | Highly Destabilizing | 0.999 | D | 0.817 | deleterious | None | None | None | None | N |
| L/V | 0.1362 | likely_benign | 0.1294 | benign | -1.173 | Destabilizing | 0.767 | D | 0.345 | neutral | N | 0.478097643 | None | None | N |
| L/W | 0.9521 | likely_pathogenic | 0.9717 | pathogenic | -1.611 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/Y | 0.9555 | likely_pathogenic | 0.9666 | pathogenic | -1.498 | Destabilizing | 1.0 | D | 0.836 | 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.