Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29346 | 88261;88262;88263 | chr2:178557118;178557117;178557116 | chr2:179421845;179421844;179421843 |
| N2AB | 27705 | 83338;83339;83340 | chr2:178557118;178557117;178557116 | chr2:179421845;179421844;179421843 |
| N2A | 26778 | 80557;80558;80559 | chr2:178557118;178557117;178557116 | chr2:179421845;179421844;179421843 |
| N2B | 20281 | 61066;61067;61068 | chr2:178557118;178557117;178557116 | chr2:179421845;179421844;179421843 |
| Novex-1 | 20406 | 61441;61442;61443 | chr2:178557118;178557117;178557116 | chr2:179421845;179421844;179421843 |
| Novex-2 | 20473 | 61642;61643;61644 | chr2:178557118;178557117;178557116 | chr2:179421845;179421844;179421843 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | -0.133 | 0.993 | N | 0.673 | 0.531 | 0.418467456957 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/A | None | -0.133 | 0.993 | N | 0.673 | 0.531 | 0.418467456957 | gnomAD-4.0.0 | 2.73718E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69846E-06 | 1.15977E-05 | 0 |
| D/G | rs374741129  |
None | 0.989 | N | 0.705 | 0.504 | 0.260249123532 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs374741129 |
None | 0.989 | N | 0.705 | 0.504 | 0.260249123532 | gnomAD-4.0.0 | 6.56953E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47003E-05 | 0 | 0 |
| D/V | rs374741129 |
0.294 | 0.997 | N | 0.759 | 0.467 | None | gnomAD-2.1.1 | 4.04E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-05 | 0 |
| D/V | rs374741129 |
0.294 | 0.997 | N | 0.759 | 0.467 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/V | rs374741129 |
0.294 | 0.997 | N | 0.759 | 0.467 | None | gnomAD-4.0.0 | 2.41699E-05 | None | None | None | None | N | None | 1.33433E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.22096E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2853 | likely_benign | 0.2122 | benign | -0.484 | Destabilizing | 0.993 | D | 0.673 | neutral | N | 0.498412961 | None | None | N |
| D/C | 0.8136 | likely_pathogenic | 0.7211 | pathogenic | 0.096 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/E | 0.2375 | likely_benign | 0.1997 | benign | -0.277 | Destabilizing | 0.977 | D | 0.408 | neutral | N | 0.455083471 | None | None | N |
| D/F | 0.8403 | likely_pathogenic | 0.7389 | pathogenic | -0.405 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | N |
| D/G | 0.2645 | likely_benign | 0.192 | benign | -0.683 | Destabilizing | 0.989 | D | 0.705 | prob.neutral | N | 0.505571007 | None | None | N |
| D/H | 0.4511 | ambiguous | 0.3572 | ambiguous | -0.363 | Destabilizing | 0.413 | N | 0.401 | neutral | N | 0.479334956 | None | None | N |
| D/I | 0.7332 | likely_pathogenic | 0.624 | pathogenic | -0.002 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | N |
| D/K | 0.6424 | likely_pathogenic | 0.5279 | ambiguous | 0.451 | Stabilizing | 0.995 | D | 0.777 | deleterious | None | None | None | None | N |
| D/L | 0.7171 | likely_pathogenic | 0.6007 | pathogenic | -0.002 | Destabilizing | 0.995 | D | 0.762 | deleterious | None | None | None | None | N |
| D/M | 0.8221 | likely_pathogenic | 0.7322 | pathogenic | 0.273 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/N | 0.129 | likely_benign | 0.104 | benign | 0.033 | Stabilizing | 0.977 | D | 0.69 | prob.neutral | N | 0.44042345 | None | None | N |
| D/P | 0.9807 | likely_pathogenic | 0.9651 | pathogenic | -0.142 | Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | N |
| D/Q | 0.5291 | ambiguous | 0.4381 | ambiguous | 0.075 | Stabilizing | 0.995 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/R | 0.6421 | likely_pathogenic | 0.5435 | ambiguous | 0.49 | Stabilizing | 0.995 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/S | 0.1915 | likely_benign | 0.1459 | benign | -0.042 | Destabilizing | 0.983 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/T | 0.4352 | ambiguous | 0.3361 | benign | 0.127 | Stabilizing | 0.998 | D | 0.791 | deleterious | None | None | None | None | N |
| D/V | 0.501 | ambiguous | 0.4048 | ambiguous | -0.142 | Destabilizing | 0.997 | D | 0.759 | deleterious | N | 0.504474928 | None | None | N |
| D/W | 0.9658 | likely_pathogenic | 0.9415 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/Y | 0.4742 | ambiguous | 0.364 | ambiguous | -0.149 | Destabilizing | 0.993 | D | 0.769 | deleterious | N | 0.490855846 | 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.