Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23750 | 71473;71474;71475 | chr2:178574884;178574883;178574882 | chr2:179439611;179439610;179439609 |
| N2AB | 22109 | 66550;66551;66552 | chr2:178574884;178574883;178574882 | chr2:179439611;179439610;179439609 |
| N2A | 21182 | 63769;63770;63771 | chr2:178574884;178574883;178574882 | chr2:179439611;179439610;179439609 |
| N2B | 14685 | 44278;44279;44280 | chr2:178574884;178574883;178574882 | chr2:179439611;179439610;179439609 |
| Novex-1 | 14810 | 44653;44654;44655 | chr2:178574884;178574883;178574882 | chr2:179439611;179439610;179439609 |
| Novex-2 | 14877 | 44854;44855;44856 | chr2:178574884;178574883;178574882 | chr2:179439611;179439610;179439609 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs1308116861  |
-2.049 | 0.865 | N | 0.621 | 0.217 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 0 |
| P/S | rs1308116861 |
-2.049 | 0.865 | N | 0.621 | 0.217 | None | gnomAD-4.0.0 | 6.84612E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99722E-07 | 0 | 0 |
| P/T | rs1308116861 |
None | 0.978 | N | 0.703 | 0.285 | 0.518970300747 | gnomAD-4.0.0 | 6.84612E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99722E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.064 | likely_benign | 0.0597 | benign | -1.693 | Destabilizing | 0.039 | N | 0.277 | neutral | N | 0.48995098 | None | None | N |
| P/C | 0.3816 | ambiguous | 0.3664 | ambiguous | -1.153 | Destabilizing | 0.998 | D | 0.816 | deleterious | None | None | None | None | N |
| P/D | 0.6608 | likely_pathogenic | 0.6549 | pathogenic | -1.7 | Destabilizing | 0.992 | D | 0.757 | deleterious | None | None | None | None | N |
| P/E | 0.3223 | likely_benign | 0.3 | benign | -1.632 | Destabilizing | 0.983 | D | 0.699 | prob.neutral | None | None | None | None | N |
| P/F | 0.5133 | ambiguous | 0.4737 | ambiguous | -1.218 | Destabilizing | 0.998 | D | 0.823 | deleterious | None | None | None | None | N |
| P/G | 0.4079 | ambiguous | 0.4055 | ambiguous | -2.072 | Highly Destabilizing | 0.895 | D | 0.639 | neutral | None | None | None | None | N |
| P/H | 0.2587 | likely_benign | 0.2383 | benign | -1.579 | Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | N |
| P/I | 0.1856 | likely_benign | 0.1589 | benign | -0.715 | Destabilizing | 0.983 | D | 0.823 | deleterious | None | None | None | None | N |
| P/K | 0.28 | likely_benign | 0.2506 | benign | -1.5 | Destabilizing | 0.983 | D | 0.71 | prob.delet. | None | None | None | None | N |
| P/L | 0.1096 | likely_benign | 0.1003 | benign | -0.715 | Destabilizing | 0.957 | D | 0.743 | deleterious | N | 0.490329776 | None | None | N |
| P/M | 0.2139 | likely_benign | 0.1895 | benign | -0.59 | Destabilizing | 0.999 | D | 0.796 | deleterious | None | None | None | None | N |
| P/N | 0.4119 | ambiguous | 0.3869 | ambiguous | -1.398 | Destabilizing | 0.992 | D | 0.823 | deleterious | None | None | None | None | N |
| P/Q | 0.1681 | likely_benign | 0.1477 | benign | -1.466 | Destabilizing | 0.989 | D | 0.807 | deleterious | N | 0.490583265 | None | None | N |
| P/R | 0.2362 | likely_benign | 0.211 | benign | -1.043 | Destabilizing | 0.978 | D | 0.81 | deleterious | N | 0.47987207 | None | None | N |
| P/S | 0.136 | likely_benign | 0.1287 | benign | -1.925 | Destabilizing | 0.865 | D | 0.621 | neutral | N | 0.484885273 | None | None | N |
| P/T | 0.0999 | likely_benign | 0.0926 | benign | -1.729 | Destabilizing | 0.978 | D | 0.703 | prob.neutral | N | 0.481188743 | None | None | N |
| P/V | 0.1332 | likely_benign | 0.1175 | benign | -1.008 | Destabilizing | 0.968 | D | 0.712 | prob.delet. | None | None | None | None | N |
| P/W | 0.806 | likely_pathogenic | 0.7857 | pathogenic | -1.47 | Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | N |
| P/Y | 0.5305 | ambiguous | 0.4896 | ambiguous | -1.166 | Destabilizing | 0.999 | D | 0.823 | 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.