Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22915 | 68968;68969;68970 | chr2:178577683;178577682;178577681 | chr2:179442410;179442409;179442408 |
| N2AB | 21274 | 64045;64046;64047 | chr2:178577683;178577682;178577681 | chr2:179442410;179442409;179442408 |
| N2A | 20347 | 61264;61265;61266 | chr2:178577683;178577682;178577681 | chr2:179442410;179442409;179442408 |
| N2B | 13850 | 41773;41774;41775 | chr2:178577683;178577682;178577681 | chr2:179442410;179442409;179442408 |
| Novex-1 | 13975 | 42148;42149;42150 | chr2:178577683;178577682;178577681 | chr2:179442410;179442409;179442408 |
| Novex-2 | 14042 | 42349;42350;42351 | chr2:178577683;178577682;178577681 | chr2:179442410;179442409;179442408 |
| 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/G | rs750315243  |
-2.246 | 1.0 | D | 0.701 | 0.587 | 0.713609137218 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| R/K | rs2154173966 |
None | 0.997 | N | 0.619 | 0.558 | 0.476127810785 | gnomAD-4.0.0 | 3.18482E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.5639E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9631 | likely_pathogenic | 0.971 | pathogenic | -2.085 | Highly Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| R/C | 0.4671 | ambiguous | 0.499 | ambiguous | -1.995 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/D | 0.9968 | likely_pathogenic | 0.9973 | pathogenic | -0.994 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/E | 0.964 | likely_pathogenic | 0.969 | pathogenic | -0.798 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| R/F | 0.9703 | likely_pathogenic | 0.974 | pathogenic | -1.409 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| R/G | 0.956 | likely_pathogenic | 0.9644 | pathogenic | -2.391 | Highly Destabilizing | 1.0 | D | 0.701 | prob.neutral | D | 0.567150887 | None | None | N |
| R/H | 0.3733 | ambiguous | 0.3842 | ambiguous | -2.369 | Highly Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/I | 0.9085 | likely_pathogenic | 0.9265 | pathogenic | -1.197 | Destabilizing | 1.0 | D | 0.831 | deleterious | D | 0.522548586 | None | None | N |
| R/K | 0.484 | ambiguous | 0.5199 | ambiguous | -1.519 | Destabilizing | 0.997 | D | 0.619 | neutral | N | 0.508897649 | None | None | N |
| R/L | 0.8759 | likely_pathogenic | 0.8952 | pathogenic | -1.197 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/M | 0.9264 | likely_pathogenic | 0.9356 | pathogenic | -1.689 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/N | 0.9811 | likely_pathogenic | 0.9844 | pathogenic | -1.326 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| R/P | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -1.483 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/Q | 0.3906 | ambiguous | 0.4118 | ambiguous | -1.231 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| R/S | 0.9726 | likely_pathogenic | 0.9774 | pathogenic | -2.203 | Highly Destabilizing | 1.0 | D | 0.699 | prob.neutral | D | 0.524355331 | None | None | N |
| R/T | 0.9529 | likely_pathogenic | 0.9625 | pathogenic | -1.813 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.518038682 | None | None | N |
| R/V | 0.9268 | likely_pathogenic | 0.9386 | pathogenic | -1.483 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/W | 0.7564 | likely_pathogenic | 0.7654 | pathogenic | -0.959 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/Y | 0.9207 | likely_pathogenic | 0.927 | pathogenic | -0.809 | Destabilizing | 1.0 | D | 0.818 | 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.