Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25152 | 75679;75680;75681 | chr2:178570678;178570677;178570676 | chr2:179435405;179435404;179435403 |
| N2AB | 23511 | 70756;70757;70758 | chr2:178570678;178570677;178570676 | chr2:179435405;179435404;179435403 |
| N2A | 22584 | 67975;67976;67977 | chr2:178570678;178570677;178570676 | chr2:179435405;179435404;179435403 |
| N2B | 16087 | 48484;48485;48486 | chr2:178570678;178570677;178570676 | chr2:179435405;179435404;179435403 |
| Novex-1 | 16212 | 48859;48860;48861 | chr2:178570678;178570677;178570676 | chr2:179435405;179435404;179435403 |
| Novex-2 | 16279 | 49060;49061;49062 | chr2:178570678;178570677;178570676 | chr2:179435405;179435404;179435403 |
| 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 | rs1467946546  |
-1.663 | 0.999 | D | 0.745 | 0.402 | 0.751155478543 | 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 |
| L/V | rs1467946546 |
None | 0.981 | N | 0.483 | 0.313 | 0.636119361578 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs1467946546 |
None | 0.981 | N | 0.483 | 0.313 | 0.636119361578 | gnomAD-4.0.0 | 1.85948E-06 | None | None | None | None | N | None | 4.0062E-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 | 0.5742 | likely_pathogenic | 0.6798 | pathogenic | -2.069 | Highly Destabilizing | 0.998 | D | 0.569 | neutral | None | None | None | None | N |
| L/C | 0.632 | likely_pathogenic | 0.7205 | pathogenic | -1.541 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| L/D | 0.9498 | likely_pathogenic | 0.9718 | pathogenic | -1.541 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| L/E | 0.8226 | likely_pathogenic | 0.8896 | pathogenic | -1.373 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/F | 0.212 | likely_benign | 0.2446 | benign | -1.162 | Destabilizing | 0.999 | D | 0.745 | deleterious | D | 0.53393191 | None | None | N |
| L/G | 0.8538 | likely_pathogenic | 0.9072 | pathogenic | -2.534 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| L/H | 0.6665 | likely_pathogenic | 0.7616 | pathogenic | -1.55 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.537182662 | None | None | N |
| L/I | 0.0761 | likely_benign | 0.0761 | benign | -0.775 | Destabilizing | 0.767 | D | 0.308 | neutral | N | 0.464490467 | None | None | N |
| L/K | 0.7306 | likely_pathogenic | 0.823 | pathogenic | -1.542 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| L/M | 0.1511 | likely_benign | 0.1757 | benign | -0.82 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| L/N | 0.827 | likely_pathogenic | 0.895 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/P | 0.7739 | likely_pathogenic | 0.8448 | pathogenic | -1.182 | Destabilizing | 1.0 | D | 0.862 | deleterious | D | 0.536929173 | None | None | N |
| L/Q | 0.5881 | likely_pathogenic | 0.6986 | pathogenic | -1.684 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/R | 0.6619 | likely_pathogenic | 0.759 | pathogenic | -1.186 | Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.536929173 | None | None | N |
| L/S | 0.784 | likely_pathogenic | 0.866 | pathogenic | -2.52 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| L/T | 0.5788 | likely_pathogenic | 0.6896 | pathogenic | -2.195 | Highly Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| L/V | 0.0996 | likely_benign | 0.1051 | benign | -1.182 | Destabilizing | 0.981 | D | 0.483 | neutral | N | 0.46668541 | None | None | N |
| L/W | 0.5183 | ambiguous | 0.5717 | pathogenic | -1.298 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| L/Y | 0.5493 | ambiguous | 0.6299 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.835 | 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.