Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25728 | 77407;77408;77409 | chr2:178568950;178568949;178568948 | chr2:179433677;179433676;179433675 |
| N2AB | 24087 | 72484;72485;72486 | chr2:178568950;178568949;178568948 | chr2:179433677;179433676;179433675 |
| N2A | 23160 | 69703;69704;69705 | chr2:178568950;178568949;178568948 | chr2:179433677;179433676;179433675 |
| N2B | 16663 | 50212;50213;50214 | chr2:178568950;178568949;178568948 | chr2:179433677;179433676;179433675 |
| Novex-1 | 16788 | 50587;50588;50589 | chr2:178568950;178568949;178568948 | chr2:179433677;179433676;179433675 |
| Novex-2 | 16855 | 50788;50789;50790 | chr2:178568950;178568949;178568948 | chr2:179433677;179433676;179433675 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1306199809  |
-0.392 | 1.0 | N | 0.808 | 0.623 | 0.419461527279 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/C | rs1306199809 |
-0.392 | 1.0 | N | 0.808 | 0.623 | 0.419461527279 | gnomAD-4.0.0 | 1.59192E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85943E-06 | 0 | 0 |
| S/G | rs1306199809 |
None | 1.0 | N | 0.605 | 0.36 | 0.28297238246 | gnomAD-4.0.0 | 1.59192E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85943E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2019 | likely_benign | 0.1961 | benign | -0.561 | Destabilizing | 0.997 | D | 0.611 | neutral | None | None | None | None | I |
| S/C | 0.2275 | likely_benign | 0.2126 | benign | -0.397 | Destabilizing | 1.0 | D | 0.808 | deleterious | N | 0.489819116 | None | None | I |
| S/D | 0.9412 | likely_pathogenic | 0.9475 | pathogenic | -0.469 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| S/E | 0.9572 | likely_pathogenic | 0.9568 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| S/F | 0.8237 | likely_pathogenic | 0.812 | pathogenic | -0.895 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| S/G | 0.343 | ambiguous | 0.3338 | benign | -0.765 | Destabilizing | 1.0 | D | 0.605 | neutral | N | 0.474933048 | None | None | I |
| S/H | 0.8932 | likely_pathogenic | 0.8916 | pathogenic | -1.325 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| S/I | 0.8731 | likely_pathogenic | 0.8357 | pathogenic | -0.137 | Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.507149675 | None | None | I |
| S/K | 0.9909 | likely_pathogenic | 0.9897 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| S/L | 0.4836 | ambiguous | 0.4372 | ambiguous | -0.137 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| S/M | 0.6441 | likely_pathogenic | 0.6346 | pathogenic | 0.274 | Stabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| S/N | 0.6749 | likely_pathogenic | 0.6695 | pathogenic | -0.615 | Destabilizing | 0.997 | D | 0.715 | prob.delet. | N | 0.50056631 | None | None | I |
| S/P | 0.9964 | likely_pathogenic | 0.9939 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| S/Q | 0.9223 | likely_pathogenic | 0.9193 | pathogenic | -0.871 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| S/R | 0.9835 | likely_pathogenic | 0.9804 | pathogenic | -0.542 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.4963988 | None | None | I |
| S/T | 0.2963 | likely_benign | 0.2803 | benign | -0.63 | Destabilizing | 0.981 | D | 0.621 | neutral | N | 0.492577366 | None | None | I |
| S/V | 0.7551 | likely_pathogenic | 0.7265 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | I |
| S/W | 0.9035 | likely_pathogenic | 0.8955 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| S/Y | 0.798 | likely_pathogenic | 0.7865 | pathogenic | -0.613 | Destabilizing | 1.0 | D | 0.837 | 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.