Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15608 | 47047;47048;47049 | chr2:178618728;178618727;178618726 | chr2:179483455;179483454;179483453 |
| N2AB | 13967 | 42124;42125;42126 | chr2:178618728;178618727;178618726 | chr2:179483455;179483454;179483453 |
| N2A | 13040 | 39343;39344;39345 | chr2:178618728;178618727;178618726 | chr2:179483455;179483454;179483453 |
| N2B | 6543 | 19852;19853;19854 | chr2:178618728;178618727;178618726 | chr2:179483455;179483454;179483453 |
| Novex-1 | 6668 | 20227;20228;20229 | chr2:178618728;178618727;178618726 | chr2:179483455;179483454;179483453 |
| Novex-2 | 6735 | 20428;20429;20430 | chr2:178618728;178618727;178618726 | chr2:179483455;179483454;179483453 |
| 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 | rs1352381229  |
-1.151 | 1.0 | D | 0.723 | 0.355 | 0.152612264143 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.13084E-04 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs1352381229 |
-1.151 | 1.0 | D | 0.723 | 0.355 | 0.152612264143 | gnomAD-4.0.0 | 6.8493E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53306E-05 | None | 0 | 0 | 0 | 0 | 0 |
| L/S | rs397517588 |
-1.644 | 1.0 | D | 0.817 | 0.657 | 0.831704679364 | gnomAD-2.1.1 | 1.86143E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.43904E-03 | None | 0 | 1.79E-05 | 0 |
| L/S | rs397517588 |
-1.644 | 1.0 | D | 0.817 | 0.657 | 0.831704679364 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 8.28157E-04 | 0 |
| L/S | rs397517588 |
-1.644 | 1.0 | D | 0.817 | 0.657 | 0.831704679364 | gnomAD-4.0.0 | 8.93353E-05 | None | None | None | None | N | None | 1.33726E-05 | 0 | None | 0 | 0 | None | 0 | 1.64853E-04 | 4.24131E-06 | 1.41727E-03 | 1.2832E-04 |
| L/V | rs1400702923 |
-0.896 | 0.999 | D | 0.508 | 0.359 | 0.371903410333 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 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 | 0.4283 | ambiguous | 0.5216 | ambiguous | -1.738 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| L/C | 0.6093 | likely_pathogenic | 0.7034 | pathogenic | -0.978 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/D | 0.9174 | likely_pathogenic | 0.9537 | pathogenic | -1.18 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| L/E | 0.6854 | likely_pathogenic | 0.7813 | pathogenic | -0.962 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| L/F | 0.1967 | likely_benign | 0.2937 | benign | -0.957 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.550000783 | None | None | N |
| L/G | 0.7762 | likely_pathogenic | 0.8537 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/H | 0.5408 | ambiguous | 0.6902 | pathogenic | -1.491 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/I | 0.0877 | likely_benign | 0.0947 | benign | -0.346 | Destabilizing | 0.999 | D | 0.505 | neutral | D | 0.538681203 | None | None | N |
| L/K | 0.6031 | likely_pathogenic | 0.6991 | pathogenic | -0.999 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| L/M | 0.1721 | likely_benign | 0.2094 | benign | -0.368 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| L/N | 0.7394 | likely_pathogenic | 0.8163 | pathogenic | -1.336 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/P | 0.7146 | likely_pathogenic | 0.8283 | pathogenic | -0.788 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| L/Q | 0.4066 | ambiguous | 0.5242 | ambiguous | -1.13 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| L/R | 0.4913 | ambiguous | 0.6219 | pathogenic | -0.939 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/S | 0.5977 | likely_pathogenic | 0.7158 | pathogenic | -2.086 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | D | 0.550545535 | None | None | N |
| L/T | 0.4639 | ambiguous | 0.5457 | ambiguous | -1.708 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/V | 0.0971 | likely_benign | 0.1092 | benign | -0.788 | Destabilizing | 0.999 | D | 0.508 | neutral | D | 0.522804957 | None | None | N |
| L/W | 0.5729 | likely_pathogenic | 0.6952 | pathogenic | -1.189 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| L/Y | 0.5683 | likely_pathogenic | 0.6893 | pathogenic | -0.855 | Destabilizing | 1.0 | D | 0.807 | 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.