Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13833 | 41722;41723;41724 | chr2:178636074;178636073;178636072 | chr2:179500801;179500800;179500799 |
| N2AB | 12192 | 36799;36800;36801 | chr2:178636074;178636073;178636072 | chr2:179500801;179500800;179500799 |
| N2A | 11265 | 34018;34019;34020 | chr2:178636074;178636073;178636072 | chr2:179500801;179500800;179500799 |
| N2B | 4768 | 14527;14528;14529 | chr2:178636074;178636073;178636072 | chr2:179500801;179500800;179500799 |
| Novex-1 | 4893 | 14902;14903;14904 | chr2:178636074;178636073;178636072 | chr2:179500801;179500800;179500799 |
| Novex-2 | 4960 | 15103;15104;15105 | chr2:178636074;178636073;178636072 | chr2:179500801;179500800;179500799 |
| 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 | rs1288508073  |
None | 0.999 | N | 0.667 | 0.151 | 0.550210968228 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs1288508073 |
None | 0.999 | N | 0.667 | 0.151 | 0.550210968228 | gnomAD-4.0.0 | 2.03017E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40999E-06 | 0 | 0 |
| L/M | None | None | 0.957 | N | 0.293 | 0.096 | 0.334659703779 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 | 0.6135 | likely_pathogenic | 0.6534 | pathogenic | -1.382 | Destabilizing | 0.997 | D | 0.527 | neutral | None | None | None | None | N |
| L/C | 0.8001 | likely_pathogenic | 0.816 | pathogenic | -0.78 | Destabilizing | 1.0 | D | 0.693 | prob.delet. | None | None | None | None | N |
| L/D | 0.8886 | likely_pathogenic | 0.9049 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| L/E | 0.7261 | likely_pathogenic | 0.7523 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.696 | prob.delet. | None | None | None | None | N |
| L/F | 0.281 | likely_benign | 0.3368 | benign | -1.021 | Destabilizing | 0.999 | D | 0.667 | prob.neutral | N | 0.32448624 | None | None | N |
| L/G | 0.781 | likely_pathogenic | 0.8095 | pathogenic | -1.65 | Destabilizing | 1.0 | D | 0.727 | deleterious | None | None | None | None | N |
| L/H | 0.4969 | ambiguous | 0.5227 | ambiguous | -0.823 | Destabilizing | 1.0 | D | 0.735 | deleterious | None | None | None | None | N |
| L/I | 0.2503 | likely_benign | 0.2729 | benign | -0.747 | Destabilizing | 0.994 | D | 0.447 | neutral | None | None | None | None | N |
| L/K | 0.4718 | ambiguous | 0.5062 | ambiguous | -0.887 | Destabilizing | 1.0 | D | 0.726 | deleterious | None | None | None | None | N |
| L/M | 0.1859 | likely_benign | 0.1879 | benign | -0.545 | Destabilizing | 0.957 | D | 0.293 | neutral | N | 0.339281375 | None | None | N |
| L/N | 0.564 | likely_pathogenic | 0.5955 | pathogenic | -0.623 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| L/P | 0.7298 | likely_pathogenic | 0.7579 | pathogenic | -0.926 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| L/Q | 0.361 | ambiguous | 0.3716 | ambiguous | -0.865 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| L/R | 0.4144 | ambiguous | 0.4438 | ambiguous | -0.242 | Destabilizing | 1.0 | D | 0.707 | prob.delet. | None | None | None | None | N |
| L/S | 0.5809 | likely_pathogenic | 0.6274 | pathogenic | -1.19 | Destabilizing | 0.999 | D | 0.722 | deleterious | N | 0.348132234 | None | None | N |
| L/T | 0.51 | ambiguous | 0.5379 | ambiguous | -1.127 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| L/V | 0.2596 | likely_benign | 0.2741 | benign | -0.926 | Destabilizing | 0.992 | D | 0.424 | neutral | N | 0.344830084 | None | None | N |
| L/W | 0.5143 | ambiguous | 0.5639 | ambiguous | -1.027 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.351326637 | None | None | N |
| L/Y | 0.6229 | likely_pathogenic | 0.6722 | pathogenic | -0.825 | Destabilizing | 1.0 | D | 0.722 | 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.