Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31568 | 94927;94928;94929 | chr2:178546726;178546725;178546724 | chr2:179411453;179411452;179411451 |
| N2AB | 29927 | 90004;90005;90006 | chr2:178546726;178546725;178546724 | chr2:179411453;179411452;179411451 |
| N2A | 29000 | 87223;87224;87225 | chr2:178546726;178546725;178546724 | chr2:179411453;179411452;179411451 |
| N2B | 22503 | 67732;67733;67734 | chr2:178546726;178546725;178546724 | chr2:179411453;179411452;179411451 |
| Novex-1 | 22628 | 68107;68108;68109 | chr2:178546726;178546725;178546724 | chr2:179411453;179411452;179411451 |
| Novex-2 | 22695 | 68308;68309;68310 | chr2:178546726;178546725;178546724 | chr2:179411453;179411452;179411451 |
| 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 | rs1431320981  |
-0.905 | 0.201 | N | 0.416 | 0.147 | 0.273938319068 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.02533E-04 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs1431320981 |
-0.905 | 0.201 | N | 0.416 | 0.147 | 0.273938319068 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92678E-04 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| F/L | rs1431320981 |
-0.905 | 0.201 | N | 0.416 | 0.147 | 0.273938319068 | gnomAD-4.0.0 | 3.84329E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.84801E-05 | None | 0 | 0 | 0 | 1.34009E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.2639 | likely_benign | 0.236 | benign | -1.889 | Destabilizing | 0.25 | N | 0.487 | neutral | None | None | None | None | N |
| F/C | 0.1301 | likely_benign | 0.1257 | benign | -1.002 | Destabilizing | 0.99 | D | 0.589 | neutral | N | 0.500375831 | None | None | N |
| F/D | 0.6437 | likely_pathogenic | 0.6121 | pathogenic | -0.395 | Destabilizing | 0.447 | N | 0.508 | neutral | None | None | None | None | N |
| F/E | 0.5592 | ambiguous | 0.5349 | ambiguous | -0.291 | Destabilizing | 0.021 | N | 0.486 | neutral | None | None | None | None | N |
| F/G | 0.6149 | likely_pathogenic | 0.5972 | pathogenic | -2.223 | Highly Destabilizing | 0.766 | D | 0.514 | neutral | None | None | None | None | N |
| F/H | 0.2453 | likely_benign | 0.2235 | benign | -0.339 | Destabilizing | 0.85 | D | 0.551 | neutral | None | None | None | None | N |
| F/I | 0.1208 | likely_benign | 0.114 | benign | -0.891 | Destabilizing | 0.173 | N | 0.345 | neutral | N | 0.468071411 | None | None | N |
| F/K | 0.5365 | ambiguous | 0.5168 | ambiguous | -1.052 | Destabilizing | 0.617 | D | 0.505 | neutral | None | None | None | None | N |
| F/L | 0.6801 | likely_pathogenic | 0.659 | pathogenic | -0.891 | Destabilizing | 0.201 | N | 0.416 | neutral | N | 0.499682397 | None | None | N |
| F/M | 0.3052 | likely_benign | 0.2872 | benign | -0.705 | Destabilizing | 0.85 | D | 0.495 | neutral | None | None | None | None | N |
| F/N | 0.2934 | likely_benign | 0.2617 | benign | -1.216 | Destabilizing | 0.92 | D | 0.575 | neutral | None | None | None | None | N |
| F/P | 0.9947 | likely_pathogenic | 0.9927 | pathogenic | -1.217 | Destabilizing | 0.972 | D | 0.579 | neutral | None | None | None | None | N |
| F/Q | 0.3991 | ambiguous | 0.379 | ambiguous | -1.213 | Destabilizing | 0.85 | D | 0.589 | neutral | None | None | None | None | N |
| F/R | 0.3939 | ambiguous | 0.3856 | ambiguous | -0.473 | Destabilizing | 0.85 | D | 0.573 | neutral | None | None | None | None | N |
| F/S | 0.1777 | likely_benign | 0.1612 | benign | -2.027 | Highly Destabilizing | 0.549 | D | 0.508 | neutral | N | 0.401072841 | None | None | N |
| F/T | 0.1978 | likely_benign | 0.1812 | benign | -1.829 | Destabilizing | 0.617 | D | 0.508 | neutral | None | None | None | None | N |
| F/V | 0.1079 | likely_benign | 0.1035 | benign | -1.217 | Destabilizing | 0.004 | N | 0.266 | neutral | N | 0.477690972 | None | None | N |
| F/W | 0.4839 | ambiguous | 0.4849 | ambiguous | 0.052 | Stabilizing | 0.972 | D | 0.493 | neutral | None | None | None | None | N |
| F/Y | 0.078 | likely_benign | 0.0756 | benign | -0.219 | Destabilizing | 0.007 | N | 0.19 | neutral | N | 0.403964004 | 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.