Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2136 | 6631;6632;6633 | chr2:178775458;178775457;178775456 | chr2:179640185;179640184;179640183 |
| N2AB | 2136 | 6631;6632;6633 | chr2:178775458;178775457;178775456 | chr2:179640185;179640184;179640183 |
| N2A | 2136 | 6631;6632;6633 | chr2:178775458;178775457;178775456 | chr2:179640185;179640184;179640183 |
| N2B | 2090 | 6493;6494;6495 | chr2:178775458;178775457;178775456 | chr2:179640185;179640184;179640183 |
| Novex-1 | 2090 | 6493;6494;6495 | chr2:178775458;178775457;178775456 | chr2:179640185;179640184;179640183 |
| Novex-2 | 2090 | 6493;6494;6495 | chr2:178775458;178775457;178775456 | chr2:179640185;179640184;179640183 |
| Novex-3 | 2136 | 6631;6632;6633 | chr2:178775458;178775457;178775456 | chr2:179640185;179640184;179640183 |
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 | rs761940711  |
-1.444 | 1.0 | D | 0.819 | 0.622 | 0.826486407297 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs761940711 |
-1.444 | 1.0 | D | 0.819 | 0.622 | 0.826486407297 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs761940711 |
-1.444 | 1.0 | D | 0.819 | 0.622 | 0.826486407297 | gnomAD-4.0.0 | 2.47854E-06 | None | None | None | None | N | None | 4.00588E-05 | 0 | None | 0 | 0 | None | 1.56226E-05 | 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 | 0.9285 | likely_pathogenic | 0.9456 | pathogenic | -2.297 | Highly Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| L/C | 0.9069 | likely_pathogenic | 0.915 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/D | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -2.622 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| L/E | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -2.401 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| L/F | 0.7184 | likely_pathogenic | 0.7566 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.667059657 | None | None | N |
| L/G | 0.988 | likely_pathogenic | 0.9897 | pathogenic | -2.694 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/H | 0.9971 | likely_pathogenic | 0.9977 | pathogenic | -2.387 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| L/I | 0.4386 | ambiguous | 0.4898 | ambiguous | -1.077 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| L/K | 0.9983 | likely_pathogenic | 0.9986 | pathogenic | -1.859 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/M | 0.3188 | likely_benign | 0.3498 | ambiguous | -1.421 | Destabilizing | 1.0 | D | 0.8 | deleterious | D | 0.539660124 | None | None | N |
| L/N | 0.9987 | likely_pathogenic | 0.9988 | pathogenic | -2.467 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/P | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -1.482 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| L/Q | 0.9956 | likely_pathogenic | 0.997 | pathogenic | -2.139 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| L/R | 0.9959 | likely_pathogenic | 0.9968 | pathogenic | -2.039 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| L/S | 0.9974 | likely_pathogenic | 0.998 | pathogenic | -2.705 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.771262935 | None | None | N |
| L/T | 0.9845 | likely_pathogenic | 0.9874 | pathogenic | -2.37 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| L/V | 0.4487 | ambiguous | 0.5004 | ambiguous | -1.482 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | D | 0.648831862 | None | None | N |
| L/W | 0.9846 | likely_pathogenic | 0.9885 | pathogenic | -1.435 | Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.771262935 | None | None | N |
| L/Y | 0.9793 | likely_pathogenic | 0.9822 | pathogenic | -1.501 | Destabilizing | 1.0 | D | 0.854 | 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.