Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29338 | 88237;88238;88239 | chr2:178557142;178557141;178557140 | chr2:179421869;179421868;179421867 |
| N2AB | 27697 | 83314;83315;83316 | chr2:178557142;178557141;178557140 | chr2:179421869;179421868;179421867 |
| N2A | 26770 | 80533;80534;80535 | chr2:178557142;178557141;178557140 | chr2:179421869;179421868;179421867 |
| N2B | 20273 | 61042;61043;61044 | chr2:178557142;178557141;178557140 | chr2:179421869;179421868;179421867 |
| Novex-1 | 20398 | 61417;61418;61419 | chr2:178557142;178557141;178557140 | chr2:179421869;179421868;179421867 |
| Novex-2 | 20465 | 61618;61619;61620 | chr2:178557142;178557141;178557140 | chr2:179421869;179421868;179421867 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs1274987792  |
-1.183 | 1.0 | D | 0.894 | 0.475 | 0.554315986709 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| P/H | rs1274987792 |
-1.183 | 1.0 | D | 0.894 | 0.475 | 0.554315986709 | gnomAD-4.0.0 | 1.59237E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85914E-06 | 0 | 0 |
| P/S | rs774162189 |
-1.582 | 0.987 | N | 0.811 | 0.435 | 0.359763055319 | gnomAD-2.1.1 | 8.5E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.396E-04 | 1.52516E-04 | 1.66556E-04 |
| P/S | rs774162189 |
-1.582 | 0.987 | N | 0.811 | 0.435 | 0.359763055319 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 2.94E-05 | 0 | 0 |
| P/S | rs774162189 |
-1.582 | 0.987 | N | 0.811 | 0.435 | 0.359763055319 | gnomAD-4.0.0 | 3.22324E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56362E-04 | 0 | 2.79736E-05 | 0 | 1.44129E-04 |
| P/T | rs774162189 |
None | 0.993 | N | 0.831 | 0.438 | 0.438913950225 | gnomAD-4.0.0 | 6.84413E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65695E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1177 | likely_benign | 0.1064 | benign | -1.6 | Destabilizing | 0.117 | N | 0.551 | neutral | N | 0.499794254 | None | None | N |
| P/C | 0.7544 | likely_pathogenic | 0.7405 | pathogenic | -1.315 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| P/D | 0.9208 | likely_pathogenic | 0.9022 | pathogenic | -2.659 | Highly Destabilizing | 0.998 | D | 0.853 | deleterious | None | None | None | None | N |
| P/E | 0.7047 | likely_pathogenic | 0.6633 | pathogenic | -2.661 | Highly Destabilizing | 0.995 | D | 0.845 | deleterious | None | None | None | None | N |
| P/F | 0.8662 | likely_pathogenic | 0.8471 | pathogenic | -1.348 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| P/G | 0.6662 | likely_pathogenic | 0.6194 | pathogenic | -1.894 | Destabilizing | 0.966 | D | 0.837 | deleterious | None | None | None | None | N |
| P/H | 0.5916 | likely_pathogenic | 0.5473 | ambiguous | -1.411 | Destabilizing | 1.0 | D | 0.894 | deleterious | D | 0.537561742 | None | None | N |
| P/I | 0.6611 | likely_pathogenic | 0.6543 | pathogenic | -0.871 | Destabilizing | 0.995 | D | 0.875 | deleterious | None | None | None | None | N |
| P/K | 0.6822 | likely_pathogenic | 0.6513 | pathogenic | -1.361 | Destabilizing | 0.995 | D | 0.847 | deleterious | None | None | None | None | N |
| P/L | 0.4306 | ambiguous | 0.4009 | ambiguous | -0.871 | Destabilizing | 0.993 | D | 0.869 | deleterious | D | 0.530560303 | None | None | N |
| P/M | 0.6229 | likely_pathogenic | 0.613 | pathogenic | -0.689 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| P/N | 0.7744 | likely_pathogenic | 0.7449 | pathogenic | -1.358 | Destabilizing | 0.998 | D | 0.871 | deleterious | None | None | None | None | N |
| P/Q | 0.418 | ambiguous | 0.3729 | ambiguous | -1.606 | Destabilizing | 0.998 | D | 0.84 | deleterious | None | None | None | None | N |
| P/R | 0.5459 | ambiguous | 0.5059 | ambiguous | -0.792 | Destabilizing | 0.997 | D | 0.877 | deleterious | N | 0.496540612 | None | None | N |
| P/S | 0.3028 | likely_benign | 0.2803 | benign | -1.705 | Destabilizing | 0.987 | D | 0.811 | deleterious | N | 0.497261401 | None | None | N |
| P/T | 0.3374 | likely_benign | 0.3055 | benign | -1.616 | Destabilizing | 0.993 | D | 0.831 | deleterious | N | 0.513924078 | None | None | N |
| P/V | 0.4847 | ambiguous | 0.4751 | ambiguous | -1.084 | Destabilizing | 0.99 | D | 0.861 | deleterious | None | None | None | None | N |
| P/W | 0.9452 | likely_pathogenic | 0.9376 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| P/Y | 0.8351 | likely_pathogenic | 0.8111 | pathogenic | -1.304 | Destabilizing | 1.0 | D | 0.905 | 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.