Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14077 | 42454;42455;42456 | chr2:178634552;178634551;178634550 | chr2:179499279;179499278;179499277 |
| N2AB | 12436 | 37531;37532;37533 | chr2:178634552;178634551;178634550 | chr2:179499279;179499278;179499277 |
| N2A | 11509 | 34750;34751;34752 | chr2:178634552;178634551;178634550 | chr2:179499279;179499278;179499277 |
| N2B | 5012 | 15259;15260;15261 | chr2:178634552;178634551;178634550 | chr2:179499279;179499278;179499277 |
| Novex-1 | 5137 | 15634;15635;15636 | chr2:178634552;178634551;178634550 | chr2:179499279;179499278;179499277 |
| Novex-2 | 5204 | 15835;15836;15837 | chr2:178634552;178634551;178634550 | chr2:179499279;179499278;179499277 |
| 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 | rs758746920  |
-1.681 | 0.994 | N | 0.761 | 0.338 | 0.582828786496 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/F | rs758746920 |
-1.681 | 0.994 | N | 0.761 | 0.338 | 0.582828786496 | gnomAD-4.0.0 | 1.36875E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31906E-05 | 0 |
| L/P | rs1325439536 |
-2.189 | 0.998 | N | 0.834 | 0.595 | 0.875711544465 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| L/P | rs1325439536 |
-2.189 | 0.998 | N | 0.834 | 0.595 | 0.875711544465 | gnomAD-4.0.0 | 1.59212E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85999E-06 | 0 | 0 |
| L/V | None | None | 0.122 | N | 0.298 | 0.179 | 0.269558022972 | gnomAD-4.0.0 | 6.84377E-07 | None | None | None | None | N | None | 2.9915E-05 | 0 | None | 0 | 0 | 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 | 0.8829 | likely_pathogenic | 0.895 | pathogenic | -2.852 | Highly Destabilizing | 0.931 | D | 0.703 | prob.neutral | None | None | None | None | N |
| L/C | 0.9238 | likely_pathogenic | 0.9243 | pathogenic | -2.237 | Highly Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| L/D | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -3.556 | Highly Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| L/E | 0.99 | likely_pathogenic | 0.991 | pathogenic | -3.321 | Highly Destabilizing | 0.999 | D | 0.833 | deleterious | None | None | None | None | N |
| L/F | 0.7788 | likely_pathogenic | 0.8239 | pathogenic | -1.546 | Destabilizing | 0.994 | D | 0.761 | deleterious | N | 0.512394281 | None | None | N |
| L/G | 0.981 | likely_pathogenic | 0.982 | pathogenic | -3.38 | Highly Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| L/H | 0.9814 | likely_pathogenic | 0.9831 | pathogenic | -2.843 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | D | 0.625013059 | None | None | N |
| L/I | 0.2848 | likely_benign | 0.2804 | benign | -1.293 | Destabilizing | 0.122 | N | 0.291 | neutral | N | 0.449833094 | None | None | N |
| L/K | 0.9839 | likely_pathogenic | 0.9823 | pathogenic | -2.23 | Highly Destabilizing | 0.999 | D | 0.792 | deleterious | None | None | None | None | N |
| L/M | 0.419 | ambiguous | 0.4128 | ambiguous | -1.386 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/N | 0.9891 | likely_pathogenic | 0.9875 | pathogenic | -2.672 | Highly Destabilizing | 0.999 | D | 0.824 | deleterious | None | None | None | None | N |
| L/P | 0.9848 | likely_pathogenic | 0.9879 | pathogenic | -1.8 | Destabilizing | 0.998 | D | 0.834 | deleterious | N | 0.51270812 | None | None | N |
| L/Q | 0.9634 | likely_pathogenic | 0.9648 | pathogenic | -2.49 | Highly Destabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | N |
| L/R | 0.9654 | likely_pathogenic | 0.9668 | pathogenic | -1.934 | Destabilizing | 0.998 | D | 0.785 | deleterious | D | 0.625013059 | None | None | N |
| L/S | 0.9724 | likely_pathogenic | 0.9757 | pathogenic | -3.272 | Highly Destabilizing | 0.996 | D | 0.789 | deleterious | None | None | None | None | N |
| L/T | 0.8661 | likely_pathogenic | 0.8468 | pathogenic | -2.907 | Highly Destabilizing | 0.97 | D | 0.753 | deleterious | None | None | None | None | N |
| L/V | 0.2716 | likely_benign | 0.2612 | benign | -1.8 | Destabilizing | 0.122 | N | 0.298 | neutral | N | 0.420687707 | None | None | N |
| L/W | 0.9748 | likely_pathogenic | 0.9816 | pathogenic | -2.036 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/Y | 0.9814 | likely_pathogenic | 0.9833 | pathogenic | -1.854 | Destabilizing | 0.999 | D | 0.775 | 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.