Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22106 | 66541;66542;66543 | chr2:178582053;178582052;178582051 | chr2:179446780;179446779;179446778 |
| N2AB | 20465 | 61618;61619;61620 | chr2:178582053;178582052;178582051 | chr2:179446780;179446779;179446778 |
| N2A | 19538 | 58837;58838;58839 | chr2:178582053;178582052;178582051 | chr2:179446780;179446779;179446778 |
| N2B | 13041 | 39346;39347;39348 | chr2:178582053;178582052;178582051 | chr2:179446780;179446779;179446778 |
| Novex-1 | 13166 | 39721;39722;39723 | chr2:178582053;178582052;178582051 | chr2:179446780;179446779;179446778 |
| Novex-2 | 13233 | 39922;39923;39924 | chr2:178582053;178582052;178582051 | chr2:179446780;179446779;179446778 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs1305235152  |
-1.012 | 0.999 | N | 0.741 | 0.419 | 0.28058544554 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/H | rs1305235152 |
-1.012 | 0.999 | N | 0.741 | 0.419 | 0.28058544554 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/H | rs1305235152 |
-1.012 | 0.999 | N | 0.741 | 0.419 | 0.28058544554 | gnomAD-4.0.0 | 1.23972E-06 | None | None | None | None | N | None | 2.6713E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/K | rs771219209 |
-0.156 | 0.977 | N | 0.617 | 0.417 | 0.203808441222 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| N/K | rs771219209 |
-0.156 | 0.977 | N | 0.617 | 0.417 | 0.203808441222 | gnomAD-4.0.0 | 3.42187E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49834E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.7414 | likely_pathogenic | 0.7228 | pathogenic | -0.759 | Destabilizing | 0.966 | D | 0.595 | neutral | None | None | None | None | N |
| N/C | 0.458 | ambiguous | 0.4518 | ambiguous | -0.051 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| N/D | 0.829 | likely_pathogenic | 0.8024 | pathogenic | -0.618 | Destabilizing | 0.977 | D | 0.549 | neutral | N | 0.471737633 | None | None | N |
| N/E | 0.9649 | likely_pathogenic | 0.9595 | pathogenic | -0.433 | Destabilizing | 0.983 | D | 0.595 | neutral | None | None | None | None | N |
| N/F | 0.954 | likely_pathogenic | 0.9417 | pathogenic | -0.331 | Destabilizing | 0.998 | D | 0.788 | deleterious | None | None | None | None | N |
| N/G | 0.6941 | likely_pathogenic | 0.6758 | pathogenic | -1.161 | Destabilizing | 0.983 | D | 0.506 | neutral | None | None | None | None | N |
| N/H | 0.5316 | ambiguous | 0.4831 | ambiguous | -0.708 | Destabilizing | 0.999 | D | 0.741 | deleterious | N | 0.470700902 | None | None | N |
| N/I | 0.7206 | likely_pathogenic | 0.7144 | pathogenic | 0.295 | Stabilizing | 0.993 | D | 0.769 | deleterious | N | 0.47906824 | None | None | N |
| N/K | 0.9795 | likely_pathogenic | 0.9772 | pathogenic | -0.123 | Destabilizing | 0.977 | D | 0.617 | neutral | N | 0.471484143 | None | None | N |
| N/L | 0.6667 | likely_pathogenic | 0.6427 | pathogenic | 0.295 | Stabilizing | 0.99 | D | 0.711 | prob.delet. | None | None | None | None | N |
| N/M | 0.7682 | likely_pathogenic | 0.7505 | pathogenic | 0.451 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| N/P | 0.9449 | likely_pathogenic | 0.9481 | pathogenic | -0.026 | Destabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | N |
| N/Q | 0.9047 | likely_pathogenic | 0.8972 | pathogenic | -0.648 | Destabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | N |
| N/R | 0.9682 | likely_pathogenic | 0.9653 | pathogenic | -0.329 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| N/S | 0.1369 | likely_benign | 0.1305 | benign | -0.984 | Destabilizing | 0.955 | D | 0.489 | neutral | N | 0.511803546 | None | None | N |
| N/T | 0.2481 | likely_benign | 0.2421 | benign | -0.586 | Destabilizing | 0.362 | N | 0.397 | neutral | N | 0.470071566 | None | None | N |
| N/V | 0.6735 | likely_pathogenic | 0.6787 | pathogenic | -0.026 | Destabilizing | 0.99 | D | 0.722 | prob.delet. | None | None | None | None | N |
| N/W | 0.9836 | likely_pathogenic | 0.9821 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| N/Y | 0.7968 | likely_pathogenic | 0.7564 | pathogenic | 0.144 | Stabilizing | 0.999 | D | 0.753 | deleterious | N | 0.520580531 | 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.