Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16623 | 50092;50093;50094 | chr2:178612854;178612853;178612852 | chr2:179477581;179477580;179477579 |
| N2AB | 14982 | 45169;45170;45171 | chr2:178612854;178612853;178612852 | chr2:179477581;179477580;179477579 |
| N2A | 14055 | 42388;42389;42390 | chr2:178612854;178612853;178612852 | chr2:179477581;179477580;179477579 |
| N2B | 7558 | 22897;22898;22899 | chr2:178612854;178612853;178612852 | chr2:179477581;179477580;179477579 |
| Novex-1 | 7683 | 23272;23273;23274 | chr2:178612854;178612853;178612852 | chr2:179477581;179477580;179477579 |
| Novex-2 | 7750 | 23473;23474;23475 | chr2:178612854;178612853;178612852 | chr2:179477581;179477580;179477579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | None | None | 0.999 | D | 0.687 | 0.555 | 0.541376754579 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs1244057905  |
-3.591 | 1.0 | D | 0.829 | 0.772 | None | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| F/S | rs1244057905 |
-3.591 | 1.0 | D | 0.829 | 0.772 | None | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/S | rs1244057905 |
-3.591 | 1.0 | D | 0.829 | 0.772 | None | gnomAD-4.0.0 | 9.92334E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.35686E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9972 | likely_pathogenic | 0.9982 | pathogenic | -2.464 | Highly Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| F/C | 0.9773 | likely_pathogenic | 0.984 | pathogenic | -1.504 | Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.777558315 | None | None | N |
| F/D | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.404 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| F/E | 0.9998 | likely_pathogenic | 0.9999 | pathogenic | -3.145 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| F/G | 0.9989 | likely_pathogenic | 0.9992 | pathogenic | -2.946 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| F/H | 0.998 | likely_pathogenic | 0.9985 | pathogenic | -2.235 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| F/I | 0.884 | likely_pathogenic | 0.9096 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.768 | deleterious | D | 0.599374824 | None | None | N |
| F/K | 0.9998 | likely_pathogenic | 0.9999 | pathogenic | -2.034 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| F/L | 0.9881 | likely_pathogenic | 0.9897 | pathogenic | -0.867 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | D | 0.592297971 | None | None | N |
| F/M | 0.9677 | likely_pathogenic | 0.9733 | pathogenic | -0.747 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| F/N | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -2.774 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| F/P | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -1.416 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| F/Q | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -2.502 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| F/R | 0.9992 | likely_pathogenic | 0.9995 | pathogenic | -2.049 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| F/S | 0.9985 | likely_pathogenic | 0.9991 | pathogenic | -3.187 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.777558315 | None | None | N |
| F/T | 0.9984 | likely_pathogenic | 0.999 | pathogenic | -2.791 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| F/V | 0.8931 | likely_pathogenic | 0.9204 | pathogenic | -1.416 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.566339142 | None | None | N |
| F/W | 0.9583 | likely_pathogenic | 0.962 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| F/Y | 0.8572 | likely_pathogenic | 0.8664 | pathogenic | -0.763 | Destabilizing | 0.999 | D | 0.601 | neutral | D | 0.613161847 | 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.