Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29194 | 87805;87806;87807 | chr2:178557774;178557773;178557772 | chr2:179422501;179422500;179422499 |
| N2AB | 27553 | 82882;82883;82884 | chr2:178557774;178557773;178557772 | chr2:179422501;179422500;179422499 |
| N2A | 26626 | 80101;80102;80103 | chr2:178557774;178557773;178557772 | chr2:179422501;179422500;179422499 |
| N2B | 20129 | 60610;60611;60612 | chr2:178557774;178557773;178557772 | chr2:179422501;179422500;179422499 |
| Novex-1 | 20254 | 60985;60986;60987 | chr2:178557774;178557773;178557772 | chr2:179422501;179422500;179422499 |
| Novex-2 | 20321 | 61186;61187;61188 | chr2:178557774;178557773;178557772 | chr2:179422501;179422500;179422499 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 1.0 | N | 0.609 | 0.408 | 0.558264529485 | 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 |
| R/S | rs754456800  |
0.114 | 1.0 | N | 0.689 | 0.358 | 0.310147130316 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/S | rs754456800 |
0.114 | 1.0 | N | 0.689 | 0.358 | 0.310147130316 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| R/T | None | None | 1.0 | N | 0.679 | 0.427 | 0.433491693731 | gnomAD-4.0.0 | 3.18207E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71566E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9243 | likely_pathogenic | 0.9474 | pathogenic | 0.129 | Stabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| R/C | 0.5509 | ambiguous | 0.6464 | pathogenic | -0.067 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| R/D | 0.9634 | likely_pathogenic | 0.9748 | pathogenic | -0.19 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/E | 0.898 | likely_pathogenic | 0.9328 | pathogenic | -0.14 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| R/F | 0.9524 | likely_pathogenic | 0.9649 | pathogenic | -0.134 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/G | 0.7579 | likely_pathogenic | 0.8169 | pathogenic | -0.031 | Destabilizing | 1.0 | D | 0.609 | neutral | N | 0.51671072 | None | None | N |
| R/H | 0.3849 | ambiguous | 0.452 | ambiguous | -0.55 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/I | 0.9356 | likely_pathogenic | 0.9528 | pathogenic | 0.509 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.486675109 | None | None | N |
| R/K | 0.3513 | ambiguous | 0.3676 | ambiguous | 0.023 | Stabilizing | 0.997 | D | 0.525 | neutral | N | 0.512456907 | None | None | N |
| R/L | 0.827 | likely_pathogenic | 0.8699 | pathogenic | 0.509 | Stabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | N |
| R/M | 0.8952 | likely_pathogenic | 0.925 | pathogenic | 0.031 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/N | 0.9486 | likely_pathogenic | 0.9635 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/P | 0.977 | likely_pathogenic | 0.9829 | pathogenic | 0.401 | Stabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/Q | 0.4159 | ambiguous | 0.5265 | ambiguous | 0.119 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/S | 0.9318 | likely_pathogenic | 0.9529 | pathogenic | -0.031 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.487675892 | None | None | N |
| R/T | 0.9028 | likely_pathogenic | 0.9297 | pathogenic | 0.132 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.508971097 | None | None | N |
| R/V | 0.9288 | likely_pathogenic | 0.9457 | pathogenic | 0.401 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/W | 0.6391 | likely_pathogenic | 0.7121 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/Y | 0.8578 | likely_pathogenic | 0.8941 | pathogenic | 0.119 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | 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.