Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33261 | 100006;100007;100008 | chr2:178537426;178537425;178537424 | chr2:179402153;179402152;179402151 |
| N2AB | 31620 | 95083;95084;95085 | chr2:178537426;178537425;178537424 | chr2:179402153;179402152;179402151 |
| N2A | 30693 | 92302;92303;92304 | chr2:178537426;178537425;178537424 | chr2:179402153;179402152;179402151 |
| N2B | 24196 | 72811;72812;72813 | chr2:178537426;178537425;178537424 | chr2:179402153;179402152;179402151 |
| Novex-1 | 24321 | 73186;73187;73188 | chr2:178537426;178537425;178537424 | chr2:179402153;179402152;179402151 |
| Novex-2 | 24388 | 73387;73388;73389 | chr2:178537426;178537425;178537424 | chr2:179402153;179402152;179402151 |
| 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 | rs1064797274  |
-0.295 | 0.998 | N | 0.612 | 0.293 | 0.442054744378 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.59E-05 | 0 |
| R/C | rs1064797274 |
-0.295 | 0.998 | N | 0.612 | 0.293 | 0.442054744378 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs1064797274 |
-0.295 | 0.998 | N | 0.612 | 0.293 | 0.442054744378 | gnomAD-4.0.0 | 8.06246E-06 | None | None | None | None | N | None | 0 | 1.6699E-05 | None | 0 | 2.23125E-05 | None | 0 | 0 | 5.93659E-06 | 0 | 6.40943E-05 |
| R/H | rs373473754 |
-0.915 | 0.01 | N | 0.191 | 0.15 | None | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 8.33E-05 | 0 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 0 |
| R/H | rs373473754 |
-0.915 | 0.01 | N | 0.191 | 0.15 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs373473754 |
-0.915 | 0.01 | N | 0.191 | 0.15 | None | gnomAD-4.0.0 | 6.2022E-06 | None | None | None | None | N | None | 4.00877E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08858E-06 | 1.10042E-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 | 0.807 | likely_pathogenic | 0.8448 | pathogenic | 0.01 | Stabilizing | 0.636 | D | 0.428 | neutral | None | None | None | None | N |
| R/C | 0.2899 | likely_benign | 0.3791 | ambiguous | -0.143 | Destabilizing | 0.998 | D | 0.612 | neutral | N | 0.477799295 | None | None | N |
| R/D | 0.9221 | likely_pathogenic | 0.9369 | pathogenic | -0.061 | Destabilizing | 0.86 | D | 0.437 | neutral | None | None | None | None | N |
| R/E | 0.7121 | likely_pathogenic | 0.7325 | pathogenic | 0.04 | Stabilizing | 0.344 | N | 0.366 | neutral | None | None | None | None | N |
| R/F | 0.8423 | likely_pathogenic | 0.9058 | pathogenic | 0.004 | Stabilizing | 0.709 | D | 0.576 | neutral | None | None | None | None | N |
| R/G | 0.632 | likely_pathogenic | 0.69 | pathogenic | -0.244 | Destabilizing | 0.77 | D | 0.413 | neutral | N | 0.477292316 | None | None | N |
| R/H | 0.1367 | likely_benign | 0.2176 | benign | -0.761 | Destabilizing | 0.01 | N | 0.191 | neutral | N | 0.477292316 | None | None | N |
| R/I | 0.7099 | likely_pathogenic | 0.7698 | pathogenic | 0.659 | Stabilizing | 0.837 | D | 0.567 | neutral | None | None | None | None | N |
| R/K | 0.2023 | likely_benign | 0.2171 | benign | -0.099 | Destabilizing | 0.079 | N | 0.388 | neutral | None | None | None | None | N |
| R/L | 0.5525 | ambiguous | 0.6211 | pathogenic | 0.659 | Stabilizing | 0.581 | D | 0.417 | neutral | N | 0.455385718 | None | None | N |
| R/M | 0.7647 | likely_pathogenic | 0.8093 | pathogenic | 0.069 | Stabilizing | 0.983 | D | 0.464 | neutral | None | None | None | None | N |
| R/N | 0.8389 | likely_pathogenic | 0.883 | pathogenic | 0.114 | Stabilizing | 0.466 | N | 0.358 | neutral | None | None | None | None | N |
| R/P | 0.7781 | likely_pathogenic | 0.7963 | pathogenic | 0.465 | Stabilizing | 0.986 | D | 0.514 | neutral | N | 0.463147626 | None | None | N |
| R/Q | 0.1895 | likely_benign | 0.2299 | benign | 0.078 | Stabilizing | 0.819 | D | 0.373 | neutral | None | None | None | None | N |
| R/S | 0.8514 | likely_pathogenic | 0.8878 | pathogenic | -0.241 | Destabilizing | 0.77 | D | 0.415 | neutral | N | 0.453147673 | None | None | N |
| R/T | 0.7798 | likely_pathogenic | 0.8282 | pathogenic | 0.017 | Stabilizing | 0.925 | D | 0.373 | neutral | None | None | None | None | N |
| R/V | 0.7972 | likely_pathogenic | 0.8399 | pathogenic | 0.465 | Stabilizing | 0.789 | D | 0.572 | neutral | None | None | None | None | N |
| R/W | 0.3544 | ambiguous | 0.4556 | ambiguous | 0.019 | Stabilizing | 0.995 | D | 0.632 | neutral | None | None | None | None | N |
| R/Y | 0.562 | ambiguous | 0.6903 | pathogenic | 0.397 | Stabilizing | 0.549 | D | 0.511 | 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.