Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15059 | 45400;45401;45402 | chr2:178621649;178621648;178621647 | chr2:179486376;179486375;179486374 |
| N2AB | 13418 | 40477;40478;40479 | chr2:178621649;178621648;178621647 | chr2:179486376;179486375;179486374 |
| N2A | 12491 | 37696;37697;37698 | chr2:178621649;178621648;178621647 | chr2:179486376;179486375;179486374 |
| N2B | 5994 | 18205;18206;18207 | chr2:178621649;178621648;178621647 | chr2:179486376;179486375;179486374 |
| Novex-1 | 6119 | 18580;18581;18582 | chr2:178621649;178621648;178621647 | chr2:179486376;179486375;179486374 |
| Novex-2 | 6186 | 18781;18782;18783 | chr2:178621649;178621648;178621647 | chr2:179486376;179486375;179486374 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs144668626  |
-1.245 | 1.0 | D | 0.745 | 0.366 | None | gnomAD-2.1.1 | 2.68029E-03 | None | None | None | None | N | None | 1.24285E-04 | 7.66697E-04 | None | 1.069E-03 | 0 | None | 1.51703E-02 | None | 4E-05 | 1.76759E-03 | 2.25861E-03 |
| A/T | rs144668626 |
-1.245 | 1.0 | D | 0.745 | 0.366 | None | gnomAD-3.1.2 | 1.58768E-03 | None | None | None | None | N | None | 1.45019E-04 | 1.70805E-03 | 0 | 8.66051E-04 | 0 | None | 0 | 0 | 1.64997E-03 | 1.8864E-02 | 1.43678E-03 |
| A/T | rs144668626 |
-1.245 | 1.0 | D | 0.745 | 0.366 | None | 1000 genomes | 3.39457E-03 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 1.43E-02 | None |
| A/T | rs144668626 |
-1.245 | 1.0 | D | 0.745 | 0.366 | None | gnomAD-4.0.0 | 1.86556E-03 | None | None | None | None | N | None | 2.00278E-04 | 9.52222E-04 | None | 8.79626E-04 | 2.23944E-05 | None | 6.25645E-05 | 3.30688E-03 | 1.11359E-03 | 1.56624E-02 | 2.33974E-03 |
| A/V | rs2154212133 |
None | 1.0 | D | 0.681 | 0.424 | 0.6184965563 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/V | rs2154212133 |
None | 1.0 | D | 0.681 | 0.424 | 0.6184965563 | gnomAD-4.0.0 | 6.58562E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47388E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5767 | likely_pathogenic | 0.645 | pathogenic | -0.841 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| A/D | 0.482 | ambiguous | 0.4989 | ambiguous | -0.688 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| A/E | 0.3933 | ambiguous | 0.4084 | ambiguous | -0.754 | Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.675194433 | None | None | N |
| A/F | 0.4971 | ambiguous | 0.5366 | ambiguous | -0.896 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| A/G | 0.2152 | likely_benign | 0.2325 | benign | -0.909 | Destabilizing | 1.0 | D | 0.596 | neutral | D | 0.57923027 | None | None | N |
| A/H | 0.6789 | likely_pathogenic | 0.7262 | pathogenic | -0.981 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| A/I | 0.2805 | likely_benign | 0.3009 | benign | -0.307 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| A/K | 0.668 | likely_pathogenic | 0.6943 | pathogenic | -1.042 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| A/L | 0.2727 | likely_benign | 0.3045 | benign | -0.307 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| A/M | 0.2844 | likely_benign | 0.3228 | benign | -0.321 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| A/N | 0.4346 | ambiguous | 0.4592 | ambiguous | -0.727 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| A/P | 0.6844 | likely_pathogenic | 0.6493 | pathogenic | -0.397 | Destabilizing | 1.0 | D | 0.8 | deleterious | N | 0.476765764 | None | None | N |
| A/Q | 0.4894 | ambiguous | 0.5369 | ambiguous | -0.9 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| A/R | 0.5978 | likely_pathogenic | 0.6253 | pathogenic | -0.663 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| A/S | 0.109 | likely_benign | 0.1176 | benign | -1.069 | Destabilizing | 1.0 | D | 0.619 | neutral | D | 0.549884581 | None | None | N |
| A/T | 0.1033 | likely_benign | 0.1088 | benign | -1.035 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.537972967 | None | None | N |
| A/V | 0.1299 | likely_benign | 0.1348 | benign | -0.397 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | D | 0.563752824 | None | None | N |
| A/W | 0.8555 | likely_pathogenic | 0.8994 | pathogenic | -1.163 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/Y | 0.6665 | likely_pathogenic | 0.7266 | pathogenic | -0.778 | Destabilizing | 1.0 | D | 0.78 | 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.