Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29487 | 88684;88685;88686 | chr2:178555000;178554999;178554998 | chr2:179419727;179419726;179419725 |
| N2AB | 27846 | 83761;83762;83763 | chr2:178555000;178554999;178554998 | chr2:179419727;179419726;179419725 |
| N2A | 26919 | 80980;80981;80982 | chr2:178555000;178554999;178554998 | chr2:179419727;179419726;179419725 |
| N2B | 20422 | 61489;61490;61491 | chr2:178555000;178554999;178554998 | chr2:179419727;179419726;179419725 |
| Novex-1 | 20547 | 61864;61865;61866 | chr2:178555000;178554999;178554998 | chr2:179419727;179419726;179419725 |
| Novex-2 | 20614 | 62065;62066;62067 | chr2:178555000;178554999;178554998 | chr2:179419727;179419726;179419725 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs2154153415  |
None | 0.165 | N | 0.589 | 0.256 | 0.680330652673 | gnomAD-4.0.0 | 2.73706E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.57691E-05 | None | 0 | 0 | 8.99468E-07 | 0 | 0 |
| V/L | rs200899806 |
-0.738 | None | N | 0.157 | 0.1 | 0.32082282376 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs200899806 |
-0.738 | None | N | 0.157 | 0.1 | 0.32082282376 | 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 |
| V/L | rs200899806 |
-0.738 | None | N | 0.157 | 0.1 | 0.32082282376 | gnomAD-4.0.0 | 6.84272E-07 | None | None | None | None | N | None | 0 | 2.23664E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | None | -0.776 | 0.457 | N | 0.653 | 0.092 | None | gnomAD-2.1.1 | 6.93754E-04 | None | None | None | None | N | None | 4.13E-05 | 1.13276E-03 | None | 8.13323E-03 | 0 | None | 0 | None | 0 | 4.3839E-04 | 1.82944E-03 |
| V/M | None | -0.776 | 0.457 | N | 0.653 | 0.092 | None | gnomAD-3.1.2 | 9.00522E-04 | None | None | None | None | N | None | 4.83E-05 | 4.45551E-03 | 0 | 1.15274E-02 | 0 | None | 0 | 0 | 3.82173E-04 | 0 | 4.78469E-04 |
| V/M | None | -0.776 | 0.457 | N | 0.653 | 0.092 | None | gnomAD-4.0.0 | 6.04261E-04 | None | None | None | None | N | None | 4.00481E-05 | 1.90089E-03 | None | 8.34459E-03 | 0 | None | 0 | 0 | 4.62796E-04 | 0 | 1.0409E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3362 | likely_benign | 0.2619 | benign | -1.978 | Destabilizing | 0.165 | N | 0.589 | neutral | N | 0.489404767 | None | None | N |
| V/C | 0.724 | likely_pathogenic | 0.6626 | pathogenic | -1.555 | Destabilizing | 0.981 | D | 0.639 | neutral | None | None | None | None | N |
| V/D | 0.7058 | likely_pathogenic | 0.5931 | pathogenic | -2.301 | Highly Destabilizing | 0.932 | D | 0.727 | prob.delet. | None | None | None | None | N |
| V/E | 0.5546 | ambiguous | 0.4375 | ambiguous | -2.204 | Highly Destabilizing | 0.773 | D | 0.68 | prob.neutral | D | 0.530848745 | None | None | N |
| V/F | 0.1882 | likely_benign | 0.1466 | benign | -1.339 | Destabilizing | 0.527 | D | 0.686 | prob.neutral | None | None | None | None | N |
| V/G | 0.4441 | ambiguous | 0.3553 | ambiguous | -2.41 | Highly Destabilizing | 0.773 | D | 0.706 | prob.neutral | D | 0.53032867 | None | None | N |
| V/H | 0.693 | likely_pathogenic | 0.5797 | pathogenic | -2.06 | Highly Destabilizing | 0.981 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/I | 0.0757 | likely_benign | 0.0744 | benign | -0.832 | Destabilizing | 0.004 | N | 0.161 | neutral | None | None | None | None | N |
| V/K | 0.6214 | likely_pathogenic | 0.4878 | ambiguous | -1.767 | Destabilizing | 0.818 | D | 0.667 | neutral | None | None | None | None | N |
| V/L | 0.165 | likely_benign | 0.1186 | benign | -0.832 | Destabilizing | None | N | 0.157 | neutral | N | 0.453635968 | None | None | N |
| V/M | 0.1773 | likely_benign | 0.1493 | benign | -0.743 | Destabilizing | 0.457 | N | 0.653 | neutral | N | 0.452483962 | None | None | N |
| V/N | 0.5409 | ambiguous | 0.4522 | ambiguous | -1.764 | Destabilizing | 0.932 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/P | 0.9328 | likely_pathogenic | 0.857 | pathogenic | -1.183 | Destabilizing | 0.932 | D | 0.689 | prob.neutral | None | None | None | None | N |
| V/Q | 0.5204 | ambiguous | 0.4044 | ambiguous | -1.806 | Destabilizing | 0.932 | D | 0.671 | neutral | None | None | None | None | N |
| V/R | 0.5379 | ambiguous | 0.4088 | ambiguous | -1.349 | Destabilizing | 0.818 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/S | 0.4126 | ambiguous | 0.3433 | ambiguous | -2.341 | Highly Destabilizing | 0.818 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/T | 0.3107 | likely_benign | 0.2655 | benign | -2.123 | Highly Destabilizing | 0.388 | N | 0.599 | neutral | None | None | None | None | N |
| V/W | 0.8174 | likely_pathogenic | 0.7091 | pathogenic | -1.703 | Destabilizing | 0.981 | D | 0.718 | prob.delet. | None | None | None | None | N |
| V/Y | 0.5505 | ambiguous | 0.4536 | ambiguous | -1.391 | Destabilizing | 0.818 | D | 0.703 | prob.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.