Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29343 | 88252;88253;88254 | chr2:178557127;178557126;178557125 | chr2:179421854;179421853;179421852 |
| N2AB | 27702 | 83329;83330;83331 | chr2:178557127;178557126;178557125 | chr2:179421854;179421853;179421852 |
| N2A | 26775 | 80548;80549;80550 | chr2:178557127;178557126;178557125 | chr2:179421854;179421853;179421852 |
| N2B | 20278 | 61057;61058;61059 | chr2:178557127;178557126;178557125 | chr2:179421854;179421853;179421852 |
| Novex-1 | 20403 | 61432;61433;61434 | chr2:178557127;178557126;178557125 | chr2:179421854;179421853;179421852 |
| Novex-2 | 20470 | 61633;61634;61635 | chr2:178557127;178557126;178557125 | chr2:179421854;179421853;179421852 |
| 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/C | None | None | 1.0 | N | 0.809 | 0.38 | 0.672407775526 | gnomAD-4.0.0 | 4.79039E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.01087E-04 | None | 0 | 0 | 2.69855E-06 | 0 | 0 |
| R/H | rs73036368  |
-1.616 | 0.999 | N | 0.611 | 0.29 | None | gnomAD-2.1.1 | 1.50565E-04 | None | None | None | None | N | None | 1.24172E-03 | 2.84E-05 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 7.07E-05 | 0 |
| R/H | rs73036368 |
-1.616 | 0.999 | N | 0.611 | 0.29 | None | gnomAD-3.1.2 | 4.53422E-04 | None | None | None | None | N | None | 1.32664E-03 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.91098E-04 | 0 | 0 |
| R/H | rs73036368 |
-1.616 | 0.999 | N | 0.611 | 0.29 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 3.8E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs73036368 |
-1.616 | 0.999 | N | 0.611 | 0.29 | None | gnomAD-4.0.0 | 1.81584E-04 | None | None | None | None | N | None | 1.55896E-03 | 3.33444E-05 | None | 0 | 0 | None | 0 | 0 | 1.33928E-04 | 3.29554E-05 | 2.08107E-04 |
| R/P | None | None | 0.996 | N | 0.831 | 0.373 | 0.524843318063 | gnomAD-4.0.0 | 6.15898E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09561E-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 | 0.4166 | ambiguous | 0.3007 | benign | -0.849 | Destabilizing | 0.807 | D | 0.611 | neutral | None | None | None | None | N |
| R/C | 0.15 | likely_benign | 0.1148 | benign | -0.832 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.475878689 | None | None | N |
| R/D | 0.6737 | likely_pathogenic | 0.5347 | ambiguous | -0.069 | Destabilizing | 0.986 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/E | 0.3654 | ambiguous | 0.2635 | benign | 0.05 | Stabilizing | 0.953 | D | 0.537 | neutral | None | None | None | None | N |
| R/F | 0.4758 | ambiguous | 0.3481 | ambiguous | -0.755 | Destabilizing | 0.998 | D | 0.821 | deleterious | None | None | None | None | N |
| R/G | 0.3419 | ambiguous | 0.2424 | benign | -1.145 | Destabilizing | 0.951 | D | 0.651 | neutral | N | 0.475118221 | None | None | N |
| R/H | 0.0908 | likely_benign | 0.0776 | benign | -1.452 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.499029036 | None | None | N |
| R/I | 0.2395 | likely_benign | 0.1799 | benign | -0.059 | Destabilizing | 0.993 | D | 0.825 | deleterious | None | None | None | None | N |
| R/K | 0.1154 | likely_benign | 0.1001 | benign | -0.838 | Destabilizing | 0.893 | D | 0.495 | neutral | None | None | None | None | N |
| R/L | 0.2557 | likely_benign | 0.1868 | benign | -0.059 | Destabilizing | 0.975 | D | 0.7 | prob.neutral | N | 0.486409243 | None | None | N |
| R/M | 0.2839 | likely_benign | 0.2142 | benign | -0.381 | Destabilizing | 0.999 | D | 0.738 | prob.delet. | None | None | None | None | N |
| R/N | 0.5207 | ambiguous | 0.3873 | ambiguous | -0.34 | Destabilizing | 0.953 | D | 0.582 | neutral | None | None | None | None | N |
| R/P | 0.9335 | likely_pathogenic | 0.8868 | pathogenic | -0.302 | Destabilizing | 0.996 | D | 0.831 | deleterious | N | 0.493982944 | None | None | N |
| R/Q | 0.0987 | likely_benign | 0.0825 | benign | -0.513 | Destabilizing | 0.993 | D | 0.601 | neutral | None | None | None | None | N |
| R/S | 0.4512 | ambiguous | 0.3239 | benign | -1.118 | Destabilizing | 0.343 | N | 0.401 | neutral | N | 0.469378133 | None | None | N |
| R/T | 0.2349 | likely_benign | 0.166 | benign | -0.819 | Destabilizing | 0.91 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/V | 0.2992 | likely_benign | 0.2287 | benign | -0.302 | Destabilizing | 0.986 | D | 0.821 | deleterious | None | None | None | None | N |
| R/W | 0.2043 | likely_benign | 0.152 | benign | -0.428 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | N |
| R/Y | 0.3468 | ambiguous | 0.2457 | benign | -0.132 | Destabilizing | 0.998 | D | 0.823 | 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.