Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30591 | 91996;91997;91998 | chr2:178550067;178550066;178550065 | chr2:179414794;179414793;179414792 |
| N2AB | 28950 | 87073;87074;87075 | chr2:178550067;178550066;178550065 | chr2:179414794;179414793;179414792 |
| N2A | 28023 | 84292;84293;84294 | chr2:178550067;178550066;178550065 | chr2:179414794;179414793;179414792 |
| N2B | 21526 | 64801;64802;64803 | chr2:178550067;178550066;178550065 | chr2:179414794;179414793;179414792 |
| Novex-1 | 21651 | 65176;65177;65178 | chr2:178550067;178550066;178550065 | chr2:179414794;179414793;179414792 |
| Novex-2 | 21718 | 65377;65378;65379 | chr2:178550067;178550066;178550065 | chr2:179414794;179414793;179414792 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs752576185  |
0.429 | 1.0 | N | 0.683 | 0.369 | 0.16115917748 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 4.65E-05 | 2.66E-05 | 1.65563E-04 |
| R/Q | rs752576185 |
0.429 | 1.0 | N | 0.683 | 0.369 | 0.16115917748 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/Q | rs752576185 |
0.429 | 1.0 | N | 0.683 | 0.369 | 0.16115917748 | gnomAD-4.0.0 | 3.78027E-05 | None | None | None | None | I | None | 5.34231E-05 | 1.667E-05 | None | 3.37906E-05 | 0 | None | 3.12471E-05 | 1.64474E-04 | 3.39047E-05 | 1.09791E-04 | 3.20236E-05 |
| R/W | rs760668673 |
-0.309 | 1.0 | N | 0.77 | 0.421 | 0.345859378078 | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 7.1E-05 | 0 |
| R/W | rs760668673 |
-0.309 | 1.0 | N | 0.77 | 0.421 | 0.345859378078 | gnomAD-4.0.0 | 1.2316E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.74546E-05 | 0 | 1.16934E-05 | 3.47842E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8301 | likely_pathogenic | 0.865 | pathogenic | -0.058 | Destabilizing | 0.999 | D | 0.588 | neutral | None | None | None | None | I |
| R/C | 0.4621 | ambiguous | 0.5279 | ambiguous | -0.205 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| R/D | 0.968 | likely_pathogenic | 0.9698 | pathogenic | -0.103 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| R/E | 0.8264 | likely_pathogenic | 0.85 | pathogenic | -0.047 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | I |
| R/F | 0.9384 | likely_pathogenic | 0.9497 | pathogenic | -0.304 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/G | 0.7804 | likely_pathogenic | 0.8139 | pathogenic | -0.241 | Destabilizing | 1.0 | D | 0.586 | neutral | N | 0.480583999 | None | None | I |
| R/H | 0.431 | ambiguous | 0.4699 | ambiguous | -0.69 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| R/I | 0.6894 | likely_pathogenic | 0.7343 | pathogenic | 0.387 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| R/K | 0.2951 | likely_benign | 0.3245 | benign | -0.128 | Destabilizing | 0.998 | D | 0.515 | neutral | None | None | None | None | I |
| R/L | 0.6874 | likely_pathogenic | 0.7271 | pathogenic | 0.387 | Stabilizing | 1.0 | D | 0.586 | neutral | N | 0.450119026 | None | None | I |
| R/M | 0.778 | likely_pathogenic | 0.8138 | pathogenic | 0.008 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/N | 0.9383 | likely_pathogenic | 0.945 | pathogenic | 0.111 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/P | 0.8825 | likely_pathogenic | 0.9069 | pathogenic | 0.259 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.493033279 | None | None | I |
| R/Q | 0.3127 | likely_benign | 0.3542 | ambiguous | -0.007 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.474392254 | None | None | I |
| R/S | 0.905 | likely_pathogenic | 0.9246 | pathogenic | -0.252 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| R/T | 0.79 | likely_pathogenic | 0.8184 | pathogenic | -0.067 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
| R/V | 0.7567 | likely_pathogenic | 0.8005 | pathogenic | 0.259 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/W | 0.538 | ambiguous | 0.5817 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.77 | deleterious | N | 0.484876413 | None | None | I |
| R/Y | 0.8496 | likely_pathogenic | 0.8654 | pathogenic | 0.05 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
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.