Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22661 | 68206;68207;68208 | chr2:178579049;178579048;178579047 | chr2:179443776;179443775;179443774 |
| N2AB | 21020 | 63283;63284;63285 | chr2:178579049;178579048;178579047 | chr2:179443776;179443775;179443774 |
| N2A | 20093 | 60502;60503;60504 | chr2:178579049;178579048;178579047 | chr2:179443776;179443775;179443774 |
| N2B | 13596 | 41011;41012;41013 | chr2:178579049;178579048;178579047 | chr2:179443776;179443775;179443774 |
| Novex-1 | 13721 | 41386;41387;41388 | chr2:178579049;178579048;178579047 | chr2:179443776;179443775;179443774 |
| Novex-2 | 13788 | 41587;41588;41589 | chr2:178579049;178579048;178579047 | chr2:179443776;179443775;179443774 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | None | None | 0.106 | N | 0.767 | 0.3 | 0.505151966591 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7993E-06 | 0 | 0 |
| M/L | rs1201216819  |
0.123 | 0.001 | N | 0.309 | 0.066 | 0.332386209738 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/L | rs1201216819 |
0.123 | 0.001 | N | 0.309 | 0.066 | 0.332386209738 | gnomAD-4.0.0 | 1.36885E-06 | None | None | None | None | N | None | 2.99061E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65739E-05 |
| M/T | rs929252811 |
None | 0.012 | N | 0.691 | 0.162 | 0.649193914283 | gnomAD-4.0.0 | 1.16351E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.5294E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4511 | ambiguous | 0.4107 | ambiguous | -1.944 | Destabilizing | 0.007 | N | 0.582 | neutral | None | None | None | None | N |
| M/C | 0.6968 | likely_pathogenic | 0.7024 | pathogenic | -2.527 | Highly Destabilizing | 0.356 | N | 0.771 | deleterious | None | None | None | None | N |
| M/D | 0.9955 | likely_pathogenic | 0.9946 | pathogenic | -2.164 | Highly Destabilizing | 0.356 | N | 0.799 | deleterious | None | None | None | None | N |
| M/E | 0.9722 | likely_pathogenic | 0.967 | pathogenic | -1.869 | Destabilizing | 0.136 | N | 0.777 | deleterious | None | None | None | None | N |
| M/F | 0.5818 | likely_pathogenic | 0.5401 | ambiguous | -0.457 | Destabilizing | 0.072 | N | 0.688 | prob.neutral | None | None | None | None | N |
| M/G | 0.8945 | likely_pathogenic | 0.8767 | pathogenic | -2.482 | Highly Destabilizing | 0.136 | N | 0.777 | deleterious | None | None | None | None | N |
| M/H | 0.9793 | likely_pathogenic | 0.9748 | pathogenic | -2.391 | Highly Destabilizing | 0.628 | D | 0.765 | deleterious | None | None | None | None | N |
| M/I | 0.1932 | likely_benign | 0.1575 | benign | -0.372 | Destabilizing | None | N | 0.209 | neutral | N | 0.383846943 | None | None | N |
| M/K | 0.9431 | likely_pathogenic | 0.9288 | pathogenic | -1.234 | Destabilizing | 0.106 | N | 0.767 | deleterious | N | 0.477415037 | None | None | N |
| M/L | 0.1513 | likely_benign | 0.1314 | benign | -0.372 | Destabilizing | 0.001 | N | 0.309 | neutral | N | 0.423117407 | None | None | N |
| M/N | 0.9577 | likely_pathogenic | 0.9493 | pathogenic | -1.855 | Destabilizing | 0.628 | D | 0.806 | deleterious | None | None | None | None | N |
| M/P | 0.9944 | likely_pathogenic | 0.9929 | pathogenic | -0.881 | Destabilizing | 0.628 | D | 0.805 | deleterious | None | None | None | None | N |
| M/Q | 0.901 | likely_pathogenic | 0.8922 | pathogenic | -1.373 | Destabilizing | 0.628 | D | 0.725 | prob.delet. | None | None | None | None | N |
| M/R | 0.9416 | likely_pathogenic | 0.9223 | pathogenic | -1.665 | Destabilizing | 0.295 | N | 0.806 | deleterious | N | 0.477415037 | None | None | N |
| M/S | 0.7988 | likely_pathogenic | 0.7791 | pathogenic | -2.317 | Highly Destabilizing | 0.072 | N | 0.739 | prob.delet. | None | None | None | None | N |
| M/T | 0.5401 | ambiguous | 0.4925 | ambiguous | -1.872 | Destabilizing | 0.012 | N | 0.691 | prob.neutral | N | 0.465387168 | None | None | N |
| M/V | 0.0649 | likely_benign | 0.0597 | benign | -0.881 | Destabilizing | None | N | 0.204 | neutral | N | 0.394389224 | None | None | N |
| M/W | 0.9752 | likely_pathogenic | 0.969 | pathogenic | -0.868 | Destabilizing | 0.864 | D | 0.751 | deleterious | None | None | None | None | N |
| M/Y | 0.9461 | likely_pathogenic | 0.9341 | pathogenic | -0.811 | Destabilizing | 0.356 | N | 0.805 | 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.