Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30206 | 90841;90842;90843 | chr2:178552284;178552283;178552282 | chr2:179417011;179417010;179417009 |
| N2AB | 28565 | 85918;85919;85920 | chr2:178552284;178552283;178552282 | chr2:179417011;179417010;179417009 |
| N2A | 27638 | 83137;83138;83139 | chr2:178552284;178552283;178552282 | chr2:179417011;179417010;179417009 |
| N2B | 21141 | 63646;63647;63648 | chr2:178552284;178552283;178552282 | chr2:179417011;179417010;179417009 |
| Novex-1 | 21266 | 64021;64022;64023 | chr2:178552284;178552283;178552282 | chr2:179417011;179417010;179417009 |
| Novex-2 | 21333 | 64222;64223;64224 | chr2:178552284;178552283;178552282 | chr2:179417011;179417010;179417009 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs373893122  |
None | 1.0 | N | 0.812 | 0.446 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/F | rs373893122 |
None | 1.0 | N | 0.812 | 0.446 | None | gnomAD-4.0.0 | 3.65721E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.74715E-05 | 0 | 4.80492E-05 |
| L/I | None | None | 0.999 | N | 0.556 | 0.373 | 0.602958996521 | 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 |
| L/I | None | None | 0.999 | N | 0.556 | 0.373 | 0.602958996521 | gnomAD-4.0.0 | 6.57376E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47003E-05 | 0 | 0 |
| L/V | rs373893122 |
-2.068 | 0.999 | N | 0.553 | 0.337 | 0.559427399277 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs373893122 |
-2.068 | 0.999 | N | 0.553 | 0.337 | 0.559427399277 | gnomAD-4.0.0 | 6.84401E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52016E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6436 | likely_pathogenic | 0.5517 | ambiguous | -2.552 | Highly Destabilizing | 0.999 | D | 0.728 | prob.delet. | None | None | None | None | N |
| L/C | 0.7979 | likely_pathogenic | 0.742 | pathogenic | -2.034 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.9984 | pathogenic | -3.091 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/E | 0.9936 | likely_pathogenic | 0.9895 | pathogenic | -2.872 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/F | 0.6308 | likely_pathogenic | 0.5551 | ambiguous | -1.568 | Destabilizing | 1.0 | D | 0.812 | deleterious | N | 0.49740471 | None | None | N |
| L/G | 0.9621 | likely_pathogenic | 0.9378 | pathogenic | -3.091 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| L/H | 0.9874 | likely_pathogenic | 0.9794 | pathogenic | -2.625 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | N | 0.516015944 | None | None | N |
| L/I | 0.1868 | likely_benign | 0.1503 | benign | -0.997 | Destabilizing | 0.999 | D | 0.556 | neutral | N | 0.519415456 | None | None | N |
| L/K | 0.992 | likely_pathogenic | 0.9877 | pathogenic | -2.01 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| L/M | 0.226 | likely_benign | 0.1851 | benign | -1.072 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| L/N | 0.9942 | likely_pathogenic | 0.9883 | pathogenic | -2.38 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| L/P | 0.9948 | likely_pathogenic | 0.9922 | pathogenic | -1.496 | Destabilizing | 1.0 | D | 0.84 | deleterious | N | 0.504406149 | None | None | N |
| L/Q | 0.9671 | likely_pathogenic | 0.947 | pathogenic | -2.251 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| L/R | 0.9796 | likely_pathogenic | 0.9734 | pathogenic | -1.71 | Destabilizing | 1.0 | D | 0.831 | deleterious | N | 0.515762455 | None | None | N |
| L/S | 0.9566 | likely_pathogenic | 0.9156 | pathogenic | -3.04 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/T | 0.8129 | likely_pathogenic | 0.7295 | pathogenic | -2.676 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/V | 0.1874 | likely_benign | 0.1547 | benign | -1.496 | Destabilizing | 0.999 | D | 0.553 | neutral | N | 0.47765926 | None | None | N |
| L/W | 0.9629 | likely_pathogenic | 0.9491 | pathogenic | -2.005 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/Y | 0.9737 | likely_pathogenic | 0.9595 | pathogenic | -1.707 | Destabilizing | 1.0 | D | 0.851 | 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.