Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22836 | 68731;68732;68733 | chr2:178578009;178578008;178578007 | chr2:179442736;179442735;179442734 |
| N2AB | 21195 | 63808;63809;63810 | chr2:178578009;178578008;178578007 | chr2:179442736;179442735;179442734 |
| N2A | 20268 | 61027;61028;61029 | chr2:178578009;178578008;178578007 | chr2:179442736;179442735;179442734 |
| N2B | 13771 | 41536;41537;41538 | chr2:178578009;178578008;178578007 | chr2:179442736;179442735;179442734 |
| Novex-1 | 13896 | 41911;41912;41913 | chr2:178578009;178578008;178578007 | chr2:179442736;179442735;179442734 |
| Novex-2 | 13963 | 42112;42113;42114 | chr2:178578009;178578008;178578007 | chr2:179442736;179442735;179442734 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs777547127  |
-1.891 | 0.005 | N | 0.271 | 0.121 | 0.51880533489 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| V/A | rs777547127 |
-1.891 | 0.005 | N | 0.271 | 0.121 | 0.51880533489 | gnomAD-4.0.0 | 4.10718E-06 | None | None | None | None | N | None | 2.99133E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49863E-06 | 0 | 0 |
| V/F | rs1422284948 |
None | 0.933 | N | 0.8 | 0.163 | 0.667047117793 | gnomAD-4.0.0 | 6.84542E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9974E-07 | 0 | 0 |
| V/I | rs1422284948 |
None | 0.451 | N | 0.645 | 0.132 | 0.395595088485 | gnomAD-4.0.0 | 3.42271E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73853E-04 | 0 | 4.64339E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1907 | likely_benign | 0.1568 | benign | -1.587 | Destabilizing | 0.005 | N | 0.271 | neutral | N | 0.513936987 | None | None | N |
| V/C | 0.6712 | likely_pathogenic | 0.6114 | pathogenic | -1.093 | Destabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| V/D | 0.766 | likely_pathogenic | 0.7182 | pathogenic | -1.587 | Destabilizing | 0.966 | D | 0.842 | deleterious | N | 0.492115931 | None | None | N |
| V/E | 0.5231 | ambiguous | 0.4906 | ambiguous | -1.433 | Destabilizing | 0.949 | D | 0.739 | deleterious | None | None | None | None | N |
| V/F | 0.2275 | likely_benign | 0.1998 | benign | -0.925 | Destabilizing | 0.933 | D | 0.8 | deleterious | N | 0.486905101 | None | None | N |
| V/G | 0.4327 | ambiguous | 0.3588 | ambiguous | -2.041 | Highly Destabilizing | 0.666 | D | 0.787 | deleterious | N | 0.492115931 | None | None | N |
| V/H | 0.6736 | likely_pathogenic | 0.6167 | pathogenic | -1.504 | Destabilizing | 0.998 | D | 0.793 | deleterious | None | None | None | None | N |
| V/I | 0.079 | likely_benign | 0.0743 | benign | -0.37 | Destabilizing | 0.451 | N | 0.645 | neutral | N | 0.431993181 | None | None | N |
| V/K | 0.4895 | ambiguous | 0.4395 | ambiguous | -1.333 | Destabilizing | 0.949 | D | 0.739 | deleterious | None | None | None | None | N |
| V/L | 0.2166 | likely_benign | 0.1771 | benign | -0.37 | Destabilizing | 0.012 | N | 0.265 | neutral | N | 0.466644472 | None | None | N |
| V/M | 0.1256 | likely_benign | 0.114 | benign | -0.378 | Destabilizing | 0.949 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/N | 0.567 | likely_pathogenic | 0.4821 | ambiguous | -1.497 | Destabilizing | 0.974 | D | 0.833 | deleterious | None | None | None | None | N |
| V/P | 0.9533 | likely_pathogenic | 0.9365 | pathogenic | -0.745 | Destabilizing | 0.974 | D | 0.819 | deleterious | None | None | None | None | N |
| V/Q | 0.4263 | ambiguous | 0.3929 | ambiguous | -1.423 | Destabilizing | 0.974 | D | 0.798 | deleterious | None | None | None | None | N |
| V/R | 0.421 | ambiguous | 0.3801 | ambiguous | -1.066 | Destabilizing | 0.974 | D | 0.844 | deleterious | None | None | None | None | N |
| V/S | 0.3522 | ambiguous | 0.283 | benign | -2.113 | Highly Destabilizing | 0.725 | D | 0.772 | deleterious | None | None | None | None | N |
| V/T | 0.1753 | likely_benign | 0.1449 | benign | -1.814 | Destabilizing | 0.841 | D | 0.628 | neutral | None | None | None | None | N |
| V/W | 0.8592 | likely_pathogenic | 0.8285 | pathogenic | -1.273 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| V/Y | 0.6377 | likely_pathogenic | 0.5953 | pathogenic | -0.887 | Destabilizing | 0.991 | D | 0.776 | 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.