Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31974 | 96145;96146;96147 | chr2:178544309;178544308;178544307 | chr2:179409036;179409035;179409034 |
| N2AB | 30333 | 91222;91223;91224 | chr2:178544309;178544308;178544307 | chr2:179409036;179409035;179409034 |
| N2A | 29406 | 88441;88442;88443 | chr2:178544309;178544308;178544307 | chr2:179409036;179409035;179409034 |
| N2B | 22909 | 68950;68951;68952 | chr2:178544309;178544308;178544307 | chr2:179409036;179409035;179409034 |
| Novex-1 | 23034 | 69325;69326;69327 | chr2:178544309;178544308;178544307 | chr2:179409036;179409035;179409034 |
| Novex-2 | 23101 | 69526;69527;69528 | chr2:178544309;178544308;178544307 | chr2:179409036;179409035;179409034 |
| 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/E | rs1239268108  |
0.11 | 0.007 | N | 0.17 | 0.106 | 0.0482279557977 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/E | rs1239268108 |
0.11 | 0.007 | N | 0.17 | 0.106 | 0.0482279557977 | gnomAD-4.0.0 | 1.59137E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02444E-05 |
| D/G | rs1441974085 |
0.075 | 0.001 | N | 0.233 | 0.208 | 0.119812018005 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/G | rs1441974085 |
0.075 | 0.001 | N | 0.233 | 0.208 | 0.119812018005 | gnomAD-4.0.0 | 1.59138E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 | 0.1012 | likely_benign | 0.0964 | benign | -0.013 | Destabilizing | 0.309 | N | 0.391 | neutral | N | 0.502976206 | None | None | N |
| D/C | 0.3806 | ambiguous | 0.3906 | ambiguous | -0.19 | Destabilizing | 0.996 | D | 0.515 | neutral | None | None | None | None | N |
| D/E | 0.1233 | likely_benign | 0.1324 | benign | -0.294 | Destabilizing | 0.007 | N | 0.17 | neutral | N | 0.465745969 | None | None | N |
| D/F | 0.4186 | ambiguous | 0.4211 | ambiguous | -0.062 | Destabilizing | 0.984 | D | 0.483 | neutral | None | None | None | None | N |
| D/G | 0.0841 | likely_benign | 0.0834 | benign | -0.14 | Destabilizing | 0.001 | N | 0.233 | neutral | N | 0.374542388 | None | None | N |
| D/H | 0.1691 | likely_benign | 0.1701 | benign | 0.52 | Stabilizing | 0.983 | D | 0.437 | neutral | N | 0.483121008 | None | None | N |
| D/I | 0.2734 | likely_benign | 0.2665 | benign | 0.257 | Stabilizing | 0.953 | D | 0.476 | neutral | None | None | None | None | N |
| D/K | 0.2242 | likely_benign | 0.2211 | benign | 0.362 | Stabilizing | 0.59 | D | 0.421 | neutral | None | None | None | None | N |
| D/L | 0.2461 | likely_benign | 0.2433 | benign | 0.257 | Stabilizing | 0.91 | D | 0.473 | neutral | None | None | None | None | N |
| D/M | 0.3822 | ambiguous | 0.4015 | ambiguous | 0.038 | Stabilizing | 0.996 | D | 0.461 | neutral | None | None | None | None | N |
| D/N | 0.0678 | likely_benign | 0.0675 | benign | 0.115 | Stabilizing | 0.684 | D | 0.433 | neutral | N | 0.414642358 | None | None | N |
| D/P | 0.6399 | likely_pathogenic | 0.6018 | pathogenic | 0.186 | Stabilizing | 0.953 | D | 0.443 | neutral | None | None | None | None | N |
| D/Q | 0.1899 | likely_benign | 0.1963 | benign | 0.122 | Stabilizing | 0.835 | D | 0.405 | neutral | None | None | None | None | N |
| D/R | 0.2623 | likely_benign | 0.2545 | benign | 0.629 | Stabilizing | 0.91 | D | 0.439 | neutral | None | None | None | None | N |
| D/S | 0.0803 | likely_benign | 0.0804 | benign | 0.012 | Stabilizing | 0.742 | D | 0.4 | neutral | None | None | None | None | N |
| D/T | 0.1513 | likely_benign | 0.1522 | benign | 0.116 | Stabilizing | 0.742 | D | 0.422 | neutral | None | None | None | None | N |
| D/V | 0.1697 | likely_benign | 0.1633 | benign | 0.186 | Stabilizing | 0.939 | D | 0.459 | neutral | N | 0.489845569 | None | None | N |
| D/W | 0.7793 | likely_pathogenic | 0.7844 | pathogenic | -0.009 | Destabilizing | 0.996 | D | 0.57 | neutral | None | None | None | None | N |
| D/Y | 0.1669 | likely_benign | 0.1603 | benign | 0.163 | Stabilizing | 0.979 | D | 0.479 | neutral | N | 0.489592079 | 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.