Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20539 | 61840;61841;61842 | chr2:178590110;178590109;178590108 | chr2:179454837;179454836;179454835 |
| N2AB | 18898 | 56917;56918;56919 | chr2:178590110;178590109;178590108 | chr2:179454837;179454836;179454835 |
| N2A | 17971 | 54136;54137;54138 | chr2:178590110;178590109;178590108 | chr2:179454837;179454836;179454835 |
| N2B | 11474 | 34645;34646;34647 | chr2:178590110;178590109;178590108 | chr2:179454837;179454836;179454835 |
| Novex-1 | 11599 | 35020;35021;35022 | chr2:178590110;178590109;178590108 | chr2:179454837;179454836;179454835 |
| Novex-2 | 11666 | 35221;35222;35223 | chr2:178590110;178590109;178590108 | chr2:179454837;179454836;179454835 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 1.0 | D | 0.543 | 0.631 | 0.724018906263 | gnomAD-4.0.0 | 1.5924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02554E-05 |
| A/T | rs754756569  |
-1.727 | 1.0 | D | 0.715 | 0.415 | 0.65076212359 | 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 |
| A/T | rs754756569 |
-1.727 | 1.0 | D | 0.715 | 0.415 | 0.65076212359 | gnomAD-4.0.0 | 3.18485E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77855E-05 | None | 0 | 0 | 0 | 0 | 3.02554E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.697 | likely_pathogenic | 0.6778 | pathogenic | -1.663 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| A/D | 0.9915 | likely_pathogenic | 0.9932 | pathogenic | -2.573 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | D | 0.545065793 | None | None | N |
| A/E | 0.9897 | likely_pathogenic | 0.9917 | pathogenic | -2.477 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| A/F | 0.989 | likely_pathogenic | 0.9916 | pathogenic | -1.098 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| A/G | 0.4734 | ambiguous | 0.5064 | ambiguous | -1.756 | Destabilizing | 1.0 | D | 0.543 | neutral | D | 0.544812303 | None | None | N |
| A/H | 0.9952 | likely_pathogenic | 0.9961 | pathogenic | -1.823 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| A/I | 0.8901 | likely_pathogenic | 0.8944 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| A/K | 0.9981 | likely_pathogenic | 0.9983 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| A/L | 0.886 | likely_pathogenic | 0.8874 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/M | 0.9093 | likely_pathogenic | 0.9128 | pathogenic | -0.692 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| A/N | 0.9697 | likely_pathogenic | 0.9744 | pathogenic | -1.675 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| A/P | 0.9579 | likely_pathogenic | 0.9462 | pathogenic | -0.741 | Destabilizing | 1.0 | D | 0.772 | deleterious | N | 0.501615581 | None | None | N |
| A/Q | 0.9883 | likely_pathogenic | 0.9898 | pathogenic | -1.697 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| A/R | 0.9943 | likely_pathogenic | 0.9947 | pathogenic | -1.338 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| A/S | 0.2249 | likely_benign | 0.2628 | benign | -2.055 | Highly Destabilizing | 1.0 | D | 0.58 | neutral | N | 0.503048855 | None | None | N |
| A/T | 0.4131 | ambiguous | 0.4737 | ambiguous | -1.859 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.530792817 | None | None | N |
| A/V | 0.5627 | ambiguous | 0.5579 | ambiguous | -0.741 | Destabilizing | 1.0 | D | 0.63 | neutral | N | 0.479587632 | None | None | N |
| A/W | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -1.613 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/Y | 0.9951 | likely_pathogenic | 0.9959 | pathogenic | -1.191 | Destabilizing | 1.0 | D | 0.755 | 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.