Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21635 | 65128;65129;65130 | chr2:178584738;178584737;178584736 | chr2:179449465;179449464;179449463 |
| N2AB | 19994 | 60205;60206;60207 | chr2:178584738;178584737;178584736 | chr2:179449465;179449464;179449463 |
| N2A | 19067 | 57424;57425;57426 | chr2:178584738;178584737;178584736 | chr2:179449465;179449464;179449463 |
| N2B | 12570 | 37933;37934;37935 | chr2:178584738;178584737;178584736 | chr2:179449465;179449464;179449463 |
| Novex-1 | 12695 | 38308;38309;38310 | chr2:178584738;178584737;178584736 | chr2:179449465;179449464;179449463 |
| Novex-2 | 12762 | 38509;38510;38511 | chr2:178584738;178584737;178584736 | chr2:179449465;179449464;179449463 |
| 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/C | rs201614524  |
-1.4 | 1.0 | N | 0.759 | 0.546 | None | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | I | None | 4.13E-05 | 2.83E-05 | None | 0 | 2.56753E-04 | None | 0 | None | 0 | 7.83E-05 | 0 |
| R/C | rs201614524 |
-1.4 | 1.0 | N | 0.759 | 0.546 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 3.87898E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs201614524 |
-1.4 | 1.0 | N | 0.759 | 0.546 | None | gnomAD-4.0.0 | 1.79751E-05 | None | None | None | None | I | None | 6.67699E-05 | 3.33511E-05 | None | 0 | 8.921E-05 | None | 0 | 0 | 1.52597E-05 | 0 | 0 |
| R/H | rs756768598 |
-1.878 | 1.0 | N | 0.838 | 0.438 | 0.328752806141 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 1.29232E-04 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| R/H | rs756768598 |
-1.878 | 1.0 | N | 0.838 | 0.438 | 0.328752806141 | gnomAD-4.0.0 | 2.53201E-05 | None | None | None | None | I | None | 2.98989E-05 | 0 | None | 0 | 2.52016E-05 | None | 0 | 1.73551E-04 | 2.42895E-05 | 3.47891E-05 | 6.62866E-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 | 0.7183 | likely_pathogenic | 0.7475 | pathogenic | -1.464 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/C | 0.1923 | likely_benign | 0.2203 | benign | -1.555 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.485095401 | None | None | I |
| R/D | 0.9709 | likely_pathogenic | 0.9767 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| R/E | 0.7872 | likely_pathogenic | 0.8079 | pathogenic | -0.62 | Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | I |
| R/F | 0.7675 | likely_pathogenic | 0.8123 | pathogenic | -0.765 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| R/G | 0.6492 | likely_pathogenic | 0.6816 | pathogenic | -1.816 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.512821215 | None | None | I |
| R/H | 0.1873 | likely_benign | 0.2531 | benign | -1.805 | Destabilizing | 1.0 | D | 0.838 | deleterious | N | 0.493956491 | None | None | I |
| R/I | 0.6618 | likely_pathogenic | 0.6946 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| R/K | 0.1631 | likely_benign | 0.1654 | benign | -1.312 | Destabilizing | 0.998 | D | 0.67 | neutral | None | None | None | None | I |
| R/L | 0.5458 | ambiguous | 0.5793 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.525042202 | None | None | I |
| R/M | 0.5004 | ambiguous | 0.5442 | ambiguous | -0.96 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | I |
| R/N | 0.8991 | likely_pathogenic | 0.9167 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | I |
| R/P | 0.9955 | likely_pathogenic | 0.9965 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.782 | deleterious | N | 0.513074704 | None | None | I |
| R/Q | 0.1701 | likely_benign | 0.1945 | benign | -1.045 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| R/S | 0.7372 | likely_pathogenic | 0.7703 | pathogenic | -1.953 | Destabilizing | 1.0 | D | 0.773 | deleterious | N | 0.458145206 | None | None | I |
| R/T | 0.5967 | likely_pathogenic | 0.6264 | pathogenic | -1.551 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| R/V | 0.7066 | likely_pathogenic | 0.7292 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| R/W | 0.3646 | ambiguous | 0.4819 | ambiguous | -0.406 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/Y | 0.6069 | likely_pathogenic | 0.6915 | pathogenic | -0.176 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
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.