Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27462 | 82609;82610;82611 | chr2:178563748;178563747;178563746 | chr2:179428475;179428474;179428473 |
| N2AB | 25821 | 77686;77687;77688 | chr2:178563748;178563747;178563746 | chr2:179428475;179428474;179428473 |
| N2A | 24894 | 74905;74906;74907 | chr2:178563748;178563747;178563746 | chr2:179428475;179428474;179428473 |
| N2B | 18397 | 55414;55415;55416 | chr2:178563748;178563747;178563746 | chr2:179428475;179428474;179428473 |
| Novex-1 | 18522 | 55789;55790;55791 | chr2:178563748;178563747;178563746 | chr2:179428475;179428474;179428473 |
| Novex-2 | 18589 | 55990;55991;55992 | chr2:178563748;178563747;178563746 | chr2:179428475;179428474;179428473 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | None | -0.4 | 0.033 | N | 0.444 | 0.234 | None | gnomAD-2.1.1 | 5.59899E-03 | None | None | None | None | N | None | 4.99752E-02 | 2.74523E-03 | None | 1.69475E-02 | 0 | None | 3.27E-05 | None | 0 | 4.06803E-04 | 4.63483E-03 |
| T/K | None | -0.4 | 0.033 | N | 0.444 | 0.234 | None | gnomAD-3.1.2 | 1.48864E-02 | None | None | None | None | N | None | 4.97994E-02 | 5.64156E-03 | 0 | 1.49942E-02 | 0 | None | 0 | 6.32911E-03 | 3.97047E-04 | 0 | 1.67464E-02 |
| T/K | None | -0.4 | 0.033 | N | 0.444 | 0.234 | None | 1000 genomes | 1.55751E-02 | None | None | None | None | N | None | 5.6E-02 | 5.8E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/K | None | -0.4 | 0.033 | N | 0.444 | 0.234 | None | gnomAD-4.0.0 | 3.24422E-03 | None | None | None | None | N | None | 5.10283E-02 | 3.9013E-03 | None | 1.683E-02 | 0 | None | 1.56255E-05 | 5.61241E-03 | 2.49206E-04 | 6.58776E-05 | 5.4741E-03 |
| T/M | rs55933739  |
0.174 | 0.082 | N | 0.541 | 0.184 | 0.204665344411 | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 2.61472E-04 | None | 0 | 6.26E-05 | 0 |
| T/M | rs55933739 |
0.174 | 0.082 | N | 0.541 | 0.184 | 0.204665344411 | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 6.21375E-04 | 0 |
| T/M | rs55933739 |
0.174 | 0.082 | N | 0.541 | 0.184 | 0.204665344411 | gnomAD-4.0.0 | 8.86194E-05 | None | None | None | None | N | None | 6.66827E-05 | 0 | None | 3.37952E-05 | 0 | None | 0 | 1.65071E-04 | 8.73068E-05 | 3.18408E-04 | 6.40246E-05 |
| T/R | rs55933739 |
0.018 | 0.076 | N | 0.547 | 0.172 | 0.1749357433 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0692 | likely_benign | 0.0708 | benign | -0.628 | Destabilizing | 0.001 | N | 0.251 | neutral | D | 0.528843016 | None | None | N |
| T/C | 0.2369 | likely_benign | 0.2716 | benign | -0.363 | Destabilizing | 0.131 | N | 0.264 | neutral | None | None | None | None | N |
| T/D | 0.3422 | ambiguous | 0.3726 | ambiguous | 0.038 | Stabilizing | 0.041 | N | 0.513 | neutral | None | None | None | None | N |
| T/E | 0.1814 | likely_benign | 0.1862 | benign | -0.009 | Destabilizing | 0.041 | N | 0.459 | neutral | None | None | None | None | N |
| T/F | 0.1055 | likely_benign | 0.115 | benign | -0.946 | Destabilizing | 0.01 | N | 0.53 | neutral | None | None | None | None | N |
| T/G | 0.2263 | likely_benign | 0.2483 | benign | -0.816 | Destabilizing | 0.017 | N | 0.456 | neutral | None | None | None | None | N |
| T/H | 0.1556 | likely_benign | 0.1729 | benign | -1.114 | Destabilizing | 0.314 | N | 0.413 | neutral | None | None | None | None | N |
| T/I | 0.0462 | likely_benign | 0.0457 | benign | -0.237 | Destabilizing | None | N | 0.105 | neutral | None | None | None | None | N |
| T/K | 0.0899 | likely_benign | 0.0901 | benign | -0.55 | Destabilizing | 0.033 | N | 0.444 | neutral | N | 0.488971239 | None | None | N |
| T/L | 0.0387 | likely_benign | 0.0386 | benign | -0.237 | Destabilizing | None | N | 0.105 | neutral | None | None | None | None | N |
| T/M | 0.0533 | likely_benign | 0.0538 | benign | 0.041 | Stabilizing | 0.082 | N | 0.541 | neutral | N | 0.489224729 | None | None | N |
| T/N | 0.1072 | likely_benign | 0.1125 | benign | -0.391 | Destabilizing | 0.115 | N | 0.327 | neutral | None | None | None | None | N |
| T/P | 0.0966 | likely_benign | 0.1006 | benign | -0.337 | Destabilizing | 0.09 | N | 0.505 | neutral | N | 0.489731708 | None | None | N |
| T/Q | 0.128 | likely_benign | 0.1354 | benign | -0.613 | Destabilizing | 0.115 | N | 0.536 | neutral | None | None | None | None | N |
| T/R | 0.0787 | likely_benign | 0.0806 | benign | -0.261 | Destabilizing | 0.076 | N | 0.547 | neutral | N | 0.499906976 | None | None | N |
| T/S | 0.1033 | likely_benign | 0.1091 | benign | -0.647 | Destabilizing | 0.007 | N | 0.263 | neutral | D | 0.529189733 | None | None | N |
| T/V | 0.0482 | likely_benign | 0.0491 | benign | -0.337 | Destabilizing | None | N | 0.061 | neutral | None | None | None | None | N |
| T/W | 0.3369 | likely_benign | 0.3806 | ambiguous | -0.893 | Destabilizing | 0.633 | D | 0.399 | neutral | None | None | None | None | N |
| T/Y | 0.1512 | likely_benign | 0.1631 | benign | -0.645 | Destabilizing | 0.041 | N | 0.603 | neutral | 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.