Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29253 | 87982;87983;87984 | chr2:178557505;178557504;178557503 | chr2:179422232;179422231;179422230 |
| N2AB | 27612 | 83059;83060;83061 | chr2:178557505;178557504;178557503 | chr2:179422232;179422231;179422230 |
| N2A | 26685 | 80278;80279;80280 | chr2:178557505;178557504;178557503 | chr2:179422232;179422231;179422230 |
| N2B | 20188 | 60787;60788;60789 | chr2:178557505;178557504;178557503 | chr2:179422232;179422231;179422230 |
| Novex-1 | 20313 | 61162;61163;61164 | chr2:178557505;178557504;178557503 | chr2:179422232;179422231;179422230 |
| Novex-2 | 20380 | 61363;61364;61365 | chr2:178557505;178557504;178557503 | chr2:179422232;179422231;179422230 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs757300589  |
-1.206 | 0.959 | N | 0.57 | 0.34 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.56E-05 | 0 |
| S/N | rs757300589 |
-1.206 | 0.959 | N | 0.57 | 0.34 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 0 | 4.57995E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78469E-04 |
| S/N | rs757300589 |
-1.206 | 0.959 | N | 0.57 | 0.34 | None | gnomAD-4.0.0 | 2.54058E-05 | None | None | None | None | N | None | 0 | 1.99973E-04 | None | 0 | 0 | None | 0 | 0 | 2.37315E-05 | 0 | 1.60113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1001 | likely_benign | 0.1032 | benign | -0.702 | Destabilizing | 0.927 | D | 0.467 | neutral | None | None | None | None | N |
| S/C | 0.1028 | likely_benign | 0.1155 | benign | -0.788 | Destabilizing | 0.144 | N | 0.487 | neutral | D | 0.528378869 | None | None | N |
| S/D | 0.6661 | likely_pathogenic | 0.6877 | pathogenic | -1.261 | Destabilizing | 0.984 | D | 0.579 | neutral | None | None | None | None | N |
| S/E | 0.7544 | likely_pathogenic | 0.7452 | pathogenic | -1.21 | Destabilizing | 0.969 | D | 0.575 | neutral | None | None | None | None | N |
| S/F | 0.2333 | likely_benign | 0.2153 | benign | -0.795 | Destabilizing | 0.995 | D | 0.754 | deleterious | None | None | None | None | N |
| S/G | 0.1159 | likely_benign | 0.1305 | benign | -0.983 | Destabilizing | 0.979 | D | 0.527 | neutral | D | 0.526165283 | None | None | N |
| S/H | 0.4462 | ambiguous | 0.4431 | ambiguous | -1.437 | Destabilizing | 0.183 | N | 0.487 | neutral | None | None | None | None | N |
| S/I | 0.3257 | likely_benign | 0.3443 | ambiguous | -0.05 | Destabilizing | 0.988 | D | 0.713 | prob.delet. | N | 0.511489132 | None | None | N |
| S/K | 0.8974 | likely_pathogenic | 0.9066 | pathogenic | -0.787 | Destabilizing | 0.984 | D | 0.581 | neutral | None | None | None | None | N |
| S/L | 0.1778 | likely_benign | 0.1863 | benign | -0.05 | Destabilizing | 0.969 | D | 0.654 | neutral | None | None | None | None | N |
| S/M | 0.1933 | likely_benign | 0.1884 | benign | 0.144 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| S/N | 0.1678 | likely_benign | 0.18 | benign | -1.056 | Destabilizing | 0.959 | D | 0.57 | neutral | N | 0.490800756 | None | None | N |
| S/P | 0.9867 | likely_pathogenic | 0.9922 | pathogenic | -0.233 | Destabilizing | 0.999 | D | 0.71 | prob.delet. | None | None | None | None | N |
| S/Q | 0.6407 | likely_pathogenic | 0.647 | pathogenic | -1.185 | Destabilizing | 0.995 | D | 0.641 | neutral | None | None | None | None | N |
| S/R | 0.8512 | likely_pathogenic | 0.8764 | pathogenic | -0.705 | Destabilizing | 0.994 | D | 0.706 | prob.neutral | N | 0.496890369 | None | None | N |
| S/T | 0.0998 | likely_benign | 0.096 | benign | -0.894 | Destabilizing | 0.238 | N | 0.329 | neutral | N | 0.490241769 | None | None | N |
| S/V | 0.2938 | likely_benign | 0.3044 | benign | -0.233 | Destabilizing | 0.969 | D | 0.674 | neutral | None | None | None | None | N |
| S/W | 0.4661 | ambiguous | 0.4685 | ambiguous | -0.863 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| S/Y | 0.2141 | likely_benign | 0.2039 | benign | -0.529 | Destabilizing | 0.991 | D | 0.759 | 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.