Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25534 | 76825;76826;76827 | chr2:178569532;178569531;178569530 | chr2:179434259;179434258;179434257 |
| N2AB | 23893 | 71902;71903;71904 | chr2:178569532;178569531;178569530 | chr2:179434259;179434258;179434257 |
| N2A | 22966 | 69121;69122;69123 | chr2:178569532;178569531;178569530 | chr2:179434259;179434258;179434257 |
| N2B | 16469 | 49630;49631;49632 | chr2:178569532;178569531;178569530 | chr2:179434259;179434258;179434257 |
| Novex-1 | 16594 | 50005;50006;50007 | chr2:178569532;178569531;178569530 | chr2:179434259;179434258;179434257 |
| Novex-2 | 16661 | 50206;50207;50208 | chr2:178569532;178569531;178569530 | chr2:179434259;179434258;179434257 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1245433477  |
None | 0.164 | D | 0.446 | 0.209 | 0.338592109245 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs1245433477 |
None | 0.164 | D | 0.446 | 0.209 | 0.338592109245 | gnomAD-4.0.0 | 6.84689E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52717E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1245433477 |
-1.394 | 0.012 | N | 0.221 | 0.06 | 0.311691414656 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/V | rs1245433477 |
-1.394 | 0.012 | N | 0.221 | 0.06 | 0.311691414656 | gnomAD-4.0.0 | 6.84689E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99831E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8597 | likely_pathogenic | 0.8935 | pathogenic | -1.931 | Destabilizing | 0.543 | D | 0.595 | neutral | None | None | None | None | N |
| I/C | 0.8663 | likely_pathogenic | 0.9034 | pathogenic | -1.361 | Destabilizing | 0.996 | D | 0.714 | prob.delet. | None | None | None | None | N |
| I/D | 0.9977 | likely_pathogenic | 0.9983 | pathogenic | -1.253 | Destabilizing | 0.984 | D | 0.8 | deleterious | None | None | None | None | N |
| I/E | 0.9907 | likely_pathogenic | 0.9927 | pathogenic | -1.147 | Destabilizing | 0.984 | D | 0.791 | deleterious | None | None | None | None | N |
| I/F | 0.2215 | likely_benign | 0.3053 | benign | -1.15 | Destabilizing | 0.004 | N | 0.313 | neutral | None | None | None | None | N |
| I/G | 0.9789 | likely_pathogenic | 0.9849 | pathogenic | -2.365 | Highly Destabilizing | 0.953 | D | 0.775 | deleterious | None | None | None | None | N |
| I/H | 0.9654 | likely_pathogenic | 0.9785 | pathogenic | -1.559 | Destabilizing | 0.996 | D | 0.787 | deleterious | None | None | None | None | N |
| I/K | 0.9687 | likely_pathogenic | 0.9782 | pathogenic | -1.384 | Destabilizing | 0.939 | D | 0.788 | deleterious | D | 0.530987236 | None | None | N |
| I/L | 0.2065 | likely_benign | 0.2466 | benign | -0.76 | Destabilizing | 0.164 | N | 0.446 | neutral | D | 0.534774485 | None | None | N |
| I/M | 0.1923 | likely_benign | 0.2401 | benign | -0.703 | Destabilizing | 0.939 | D | 0.624 | neutral | N | 0.512376002 | None | None | N |
| I/N | 0.9599 | likely_pathogenic | 0.9729 | pathogenic | -1.407 | Destabilizing | 0.984 | D | 0.807 | deleterious | None | None | None | None | N |
| I/P | 0.9911 | likely_pathogenic | 0.9928 | pathogenic | -1.121 | Destabilizing | 0.984 | D | 0.807 | deleterious | None | None | None | None | N |
| I/Q | 0.9669 | likely_pathogenic | 0.977 | pathogenic | -1.418 | Destabilizing | 0.984 | D | 0.802 | deleterious | None | None | None | None | N |
| I/R | 0.9475 | likely_pathogenic | 0.9644 | pathogenic | -0.947 | Destabilizing | 0.979 | D | 0.807 | deleterious | D | 0.530987236 | None | None | N |
| I/S | 0.9153 | likely_pathogenic | 0.9364 | pathogenic | -2.156 | Highly Destabilizing | 0.854 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/T | 0.865 | likely_pathogenic | 0.8936 | pathogenic | -1.908 | Destabilizing | 0.684 | D | 0.657 | neutral | N | 0.491358458 | None | None | N |
| I/V | 0.0892 | likely_benign | 0.0957 | benign | -1.121 | Destabilizing | 0.012 | N | 0.221 | neutral | N | 0.423824776 | None | None | N |
| I/W | 0.9504 | likely_pathogenic | 0.9679 | pathogenic | -1.303 | Destabilizing | 0.996 | D | 0.785 | deleterious | None | None | None | None | N |
| I/Y | 0.821 | likely_pathogenic | 0.8753 | pathogenic | -1.05 | Destabilizing | 0.59 | D | 0.697 | prob.neutral | 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.