Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21444 | 64555;64556;64557 | chr2:178586571;178586570;178586569 | chr2:179451298;179451297;179451296 |
| N2AB | 19803 | 59632;59633;59634 | chr2:178586571;178586570;178586569 | chr2:179451298;179451297;179451296 |
| N2A | 18876 | 56851;56852;56853 | chr2:178586571;178586570;178586569 | chr2:179451298;179451297;179451296 |
| N2B | 12379 | 37360;37361;37362 | chr2:178586571;178586570;178586569 | chr2:179451298;179451297;179451296 |
| Novex-1 | 12504 | 37735;37736;37737 | chr2:178586571;178586570;178586569 | chr2:179451298;179451297;179451296 |
| Novex-2 | 12571 | 37936;37937;37938 | chr2:178586571;178586570;178586569 | chr2:179451298;179451297;179451296 |
| 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/I | rs775693601  |
-0.524 | 1.0 | N | 0.825 | 0.39 | 0.659830528944 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| R/I | rs775693601 |
-0.524 | 1.0 | N | 0.825 | 0.39 | 0.659830528944 | gnomAD-4.0.0 | 1.59253E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77793E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs775693601 |
-1.364 | 0.997 | N | 0.465 | 0.31 | 0.289474373501 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs775693601 |
-1.364 | 0.997 | N | 0.465 | 0.31 | 0.289474373501 | gnomAD-4.0.0 | 1.59253E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43308E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8948 | likely_pathogenic | 0.8508 | pathogenic | -1.423 | Destabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | I |
| R/C | 0.4286 | ambiguous | 0.3585 | ambiguous | -1.473 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| R/D | 0.9863 | likely_pathogenic | 0.981 | pathogenic | -0.368 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| R/E | 0.7864 | likely_pathogenic | 0.7316 | pathogenic | -0.21 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | I |
| R/F | 0.8885 | likely_pathogenic | 0.8369 | pathogenic | -1.111 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | I |
| R/G | 0.8801 | likely_pathogenic | 0.8298 | pathogenic | -1.759 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.476030047 | None | None | I |
| R/H | 0.2757 | likely_benign | 0.2232 | benign | -1.798 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| R/I | 0.635 | likely_pathogenic | 0.539 | ambiguous | -0.492 | Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.467071334 | None | None | I |
| R/K | 0.1392 | likely_benign | 0.1214 | benign | -1.332 | Destabilizing | 0.997 | D | 0.465 | neutral | N | 0.453662106 | None | None | I |
| R/L | 0.6483 | likely_pathogenic | 0.5657 | pathogenic | -0.492 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| R/M | 0.7022 | likely_pathogenic | 0.5947 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| R/N | 0.9574 | likely_pathogenic | 0.9405 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| R/P | 0.9953 | likely_pathogenic | 0.9933 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| R/Q | 0.2118 | likely_benign | 0.1779 | benign | -1.011 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| R/S | 0.9299 | likely_pathogenic | 0.899 | pathogenic | -1.835 | Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.524138125 | None | None | I |
| R/T | 0.7275 | likely_pathogenic | 0.6426 | pathogenic | -1.474 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.495682087 | None | None | I |
| R/V | 0.6402 | likely_pathogenic | 0.5676 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| R/W | 0.4819 | ambiguous | 0.3894 | ambiguous | -0.623 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| R/Y | 0.791 | likely_pathogenic | 0.7175 | pathogenic | -0.387 | Destabilizing | 1.0 | D | 0.82 | 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.