Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15470 | 46633;46634;46635 | chr2:178620009;178620008;178620007 | chr2:179484736;179484735;179484734 |
| N2AB | 13829 | 41710;41711;41712 | chr2:178620009;178620008;178620007 | chr2:179484736;179484735;179484734 |
| N2A | 12902 | 38929;38930;38931 | chr2:178620009;178620008;178620007 | chr2:179484736;179484735;179484734 |
| N2B | 6405 | 19438;19439;19440 | chr2:178620009;178620008;178620007 | chr2:179484736;179484735;179484734 |
| Novex-1 | 6530 | 19813;19814;19815 | chr2:178620009;178620008;178620007 | chr2:179484736;179484735;179484734 |
| Novex-2 | 6597 | 20014;20015;20016 | chr2:178620009;178620008;178620007 | chr2:179484736;179484735;179484734 |
| 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/C | rs373502448  |
-0.287 | 1.0 | D | 0.741 | 0.629 | None | gnomAD-2.1.1 | 8.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12982E-04 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs373502448 |
-0.287 | 1.0 | D | 0.741 | 0.629 | None | gnomAD-4.0.0 | 1.44039E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.575E-05 | 0 | 0 |
| R/H | rs769044716 |
-1.104 | 1.0 | D | 0.756 | 0.504 | None | gnomAD-2.1.1 | 2.04E-05 | None | None | None | None | N | None | 6.5E-05 | 2.94E-05 | None | 0 | 0 | None | 0 | None | 4.67E-05 | 1.81E-05 | 0 |
| R/H | rs769044716 |
-1.104 | 1.0 | D | 0.756 | 0.504 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| R/H | rs769044716 |
-1.104 | 1.0 | D | 0.756 | 0.504 | None | gnomAD-4.0.0 | 1.1177E-05 | None | None | None | None | N | None | 2.67795E-05 | 1.67813E-05 | None | 0 | 2.24165E-05 | None | 0 | 0 | 1.1031E-05 | 1.10632E-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 | 0.7456 | likely_pathogenic | 0.7201 | pathogenic | -0.303 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/C | 0.5042 | ambiguous | 0.4539 | ambiguous | -0.334 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.608249213 | None | None | N |
| R/D | 0.9349 | likely_pathogenic | 0.9208 | pathogenic | 0.012 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/E | 0.7339 | likely_pathogenic | 0.6979 | pathogenic | 0.098 | Stabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/F | 0.8052 | likely_pathogenic | 0.786 | pathogenic | -0.365 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/G | 0.6677 | likely_pathogenic | 0.6286 | pathogenic | -0.549 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | D | 0.608818978 | None | None | N |
| R/H | 0.1966 | likely_benign | 0.1665 | benign | -0.935 | Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.546143111 | None | None | N |
| R/I | 0.6083 | likely_pathogenic | 0.5966 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/K | 0.1742 | likely_benign | 0.1725 | benign | -0.337 | Destabilizing | 0.998 | D | 0.577 | neutral | None | None | None | None | N |
| R/L | 0.6083 | likely_pathogenic | 0.5836 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | D | 0.547030177 | None | None | N |
| R/M | 0.6463 | likely_pathogenic | 0.6095 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/N | 0.8543 | likely_pathogenic | 0.8337 | pathogenic | 0.064 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/P | 0.9296 | likely_pathogenic | 0.9409 | pathogenic | 0.138 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | D | 0.5437546 | None | None | N |
| R/Q | 0.2492 | likely_benign | 0.2221 | benign | -0.095 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/S | 0.7757 | likely_pathogenic | 0.7378 | pathogenic | -0.489 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.441570958 | None | None | N |
| R/T | 0.5403 | ambiguous | 0.4771 | ambiguous | -0.249 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| R/V | 0.6382 | likely_pathogenic | 0.6326 | pathogenic | 0.138 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/W | 0.4483 | ambiguous | 0.3984 | ambiguous | -0.237 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/Y | 0.7231 | likely_pathogenic | 0.6912 | pathogenic | 0.122 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | 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.