Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23767 | 71524;71525;71526 | chr2:178574833;178574832;178574831 | chr2:179439560;179439559;179439558 |
| N2AB | 22126 | 66601;66602;66603 | chr2:178574833;178574832;178574831 | chr2:179439560;179439559;179439558 |
| N2A | 21199 | 63820;63821;63822 | chr2:178574833;178574832;178574831 | chr2:179439560;179439559;179439558 |
| N2B | 14702 | 44329;44330;44331 | chr2:178574833;178574832;178574831 | chr2:179439560;179439559;179439558 |
| Novex-1 | 14827 | 44704;44705;44706 | chr2:178574833;178574832;178574831 | chr2:179439560;179439559;179439558 |
| Novex-2 | 14894 | 44905;44906;44907 | chr2:178574833;178574832;178574831 | chr2:179439560;179439559;179439558 |
| 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 | rs370516890  |
-1.456 | 1.0 | N | 0.677 | 0.451 | None | gnomAD-2.1.1 | 1.07924E-04 | None | None | None | None | N | None | 1.6592E-04 | 0 | None | 0 | 5.19E-05 | None | 6.55E-05 | None | 4.01E-05 | 1.73831E-04 | 0 |
| R/Q | rs370516890 |
-1.456 | 1.0 | N | 0.677 | 0.451 | None | gnomAD-3.1.2 | 1.18429E-04 | None | None | None | None | N | None | 2.17381E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.17661E-04 | 0 | 0 |
| R/Q | rs370516890 |
-1.456 | 1.0 | N | 0.677 | 0.451 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs370516890 |
-1.456 | 1.0 | N | 0.677 | 0.451 | None | gnomAD-4.0.0 | 1.09125E-04 | None | None | None | None | N | None | 1.60034E-04 | 1.66789E-05 | None | 0 | 0 | None | 1.56514E-05 | 0 | 1.2634E-04 | 7.69197E-05 | 9.61138E-05 |
| R/W | rs532157196 |
-1.141 | 1.0 | N | 0.888 | 0.563 | 0.465806656444 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9E-06 | 0 |
| R/W | rs532157196 |
-1.141 | 1.0 | N | 0.888 | 0.563 | 0.465806656444 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs532157196 |
-1.141 | 1.0 | N | 0.888 | 0.563 | 0.465806656444 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/W | rs532157196 |
-1.141 | 1.0 | N | 0.888 | 0.563 | 0.465806656444 | gnomAD-4.0.0 | 5.58005E-06 | None | None | None | None | N | None | 4.00053E-05 | 0 | None | 0 | 2.23884E-05 | None | 0 | 0 | 3.39164E-06 | 0 | 1.60174E-05 |
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 | 0.9767 | likely_pathogenic | 0.9802 | pathogenic | -2.104 | Highly Destabilizing | 0.999 | D | 0.561 | neutral | None | None | None | None | N |
| R/C | 0.462 | ambiguous | 0.4877 | ambiguous | -2.201 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| R/D | 0.9981 | likely_pathogenic | 0.9982 | pathogenic | -0.938 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| R/E | 0.9684 | likely_pathogenic | 0.9683 | pathogenic | -0.785 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| R/F | 0.983 | likely_pathogenic | 0.9839 | pathogenic | -1.879 | Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| R/G | 0.9616 | likely_pathogenic | 0.9646 | pathogenic | -2.39 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.500414952 | None | None | N |
| R/H | 0.5805 | likely_pathogenic | 0.6096 | pathogenic | -2.275 | Highly Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| R/I | 0.9544 | likely_pathogenic | 0.961 | pathogenic | -1.294 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| R/K | 0.3461 | ambiguous | 0.3678 | ambiguous | -1.773 | Destabilizing | 0.998 | D | 0.466 | neutral | None | None | None | None | N |
| R/L | 0.8784 | likely_pathogenic | 0.8895 | pathogenic | -1.294 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.488298178 | None | None | N |
| R/M | 0.9033 | likely_pathogenic | 0.9212 | pathogenic | -1.547 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| R/N | 0.9894 | likely_pathogenic | 0.9907 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.895 | deleterious | N | 0.514658094 | None | None | N |
| R/Q | 0.3939 | ambiguous | 0.4265 | ambiguous | -1.536 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.476470893 | None | None | N |
| R/S | 0.9874 | likely_pathogenic | 0.9895 | pathogenic | -2.379 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/T | 0.9786 | likely_pathogenic | 0.9828 | pathogenic | -2.04 | Highly Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| R/V | 0.9605 | likely_pathogenic | 0.9657 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| R/W | 0.8951 | likely_pathogenic | 0.9041 | pathogenic | -1.344 | Destabilizing | 1.0 | D | 0.888 | deleterious | N | 0.491994708 | None | None | N |
| R/Y | 0.9465 | likely_pathogenic | 0.9517 | pathogenic | -1.137 | Destabilizing | 1.0 | D | 0.92 | 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.