Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23047 | 69364;69365;69366 | chr2:178577196;178577195;178577194 | chr2:179441923;179441922;179441921 |
| N2AB | 21406 | 64441;64442;64443 | chr2:178577196;178577195;178577194 | chr2:179441923;179441922;179441921 |
| N2A | 20479 | 61660;61661;61662 | chr2:178577196;178577195;178577194 | chr2:179441923;179441922;179441921 |
| N2B | 13982 | 42169;42170;42171 | chr2:178577196;178577195;178577194 | chr2:179441923;179441922;179441921 |
| Novex-1 | 14107 | 42544;42545;42546 | chr2:178577196;178577195;178577194 | chr2:179441923;179441922;179441921 |
| Novex-2 | 14174 | 42745;42746;42747 | chr2:178577196;178577195;178577194 | chr2:179441923;179441922;179441921 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs368697152  |
-2.08 | 0.052 | D | 0.665 | 0.27 | None | gnomAD-2.1.1 | 5.02E-05 | None | None | None | None | I | None | 5.3799E-04 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs368697152 |
-2.08 | 0.052 | D | 0.665 | 0.27 | None | gnomAD-3.1.2 | 2.04023E-04 | None | None | None | None | I | None | 7.24568E-04 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs368697152 |
-2.08 | 0.052 | D | 0.665 | 0.27 | None | gnomAD-4.0.0 | 4.58808E-05 | None | None | None | None | I | None | 6.81345E-04 | 3.3379E-05 | None | 0 | 0 | None | 0 | 0 | 1.61089E-05 | 1.0983E-05 | 1.60231E-05 |
| V/F | None | None | 0.317 | N | 0.76 | 0.147 | 0.358340041657 | gnomAD-4.0.0 | 6.84505E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9969E-07 | 0 | 0 |
| V/I | rs2154173593 |
None | None | N | 0.251 | 0.086 | 0.246215685461 | gnomAD-4.0.0 | 6.84505E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9969E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3952 | ambiguous | 0.4181 | ambiguous | -1.995 | Destabilizing | 0.052 | N | 0.665 | neutral | D | 0.522314115 | None | None | I |
| V/C | 0.7953 | likely_pathogenic | 0.8063 | pathogenic | -1.712 | Destabilizing | 0.935 | D | 0.709 | prob.delet. | None | None | None | None | I |
| V/D | 0.9761 | likely_pathogenic | 0.9737 | pathogenic | -2.51 | Highly Destabilizing | 0.484 | N | 0.817 | deleterious | N | 0.518852057 | None | None | I |
| V/E | 0.9404 | likely_pathogenic | 0.926 | pathogenic | -2.309 | Highly Destabilizing | 0.555 | D | 0.764 | deleterious | None | None | None | None | I |
| V/F | 0.3631 | ambiguous | 0.3448 | ambiguous | -1.139 | Destabilizing | 0.317 | N | 0.76 | deleterious | N | 0.521620681 | None | None | I |
| V/G | 0.7427 | likely_pathogenic | 0.7367 | pathogenic | -2.516 | Highly Destabilizing | 0.484 | N | 0.789 | deleterious | N | 0.519612525 | None | None | I |
| V/H | 0.9713 | likely_pathogenic | 0.9624 | pathogenic | -2.284 | Highly Destabilizing | 0.935 | D | 0.803 | deleterious | None | None | None | None | I |
| V/I | 0.0566 | likely_benign | 0.0553 | benign | -0.553 | Destabilizing | None | N | 0.251 | neutral | N | 0.448373716 | None | None | I |
| V/K | 0.954 | likely_pathogenic | 0.9345 | pathogenic | -1.639 | Destabilizing | 0.555 | D | 0.764 | deleterious | None | None | None | None | I |
| V/L | 0.1071 | likely_benign | 0.0968 | benign | -0.553 | Destabilizing | 0.004 | N | 0.459 | neutral | N | 0.38593003 | None | None | I |
| V/M | 0.139 | likely_benign | 0.1287 | benign | -0.773 | Destabilizing | 0.38 | N | 0.671 | neutral | None | None | None | None | I |
| V/N | 0.9048 | likely_pathogenic | 0.8885 | pathogenic | -1.895 | Destabilizing | 0.791 | D | 0.824 | deleterious | None | None | None | None | I |
| V/P | 0.6742 | likely_pathogenic | 0.7262 | pathogenic | -1.005 | Destabilizing | 0.791 | D | 0.781 | deleterious | None | None | None | None | I |
| V/Q | 0.9321 | likely_pathogenic | 0.9121 | pathogenic | -1.761 | Destabilizing | 0.791 | D | 0.775 | deleterious | None | None | None | None | I |
| V/R | 0.9303 | likely_pathogenic | 0.9056 | pathogenic | -1.504 | Destabilizing | 0.555 | D | 0.822 | deleterious | None | None | None | None | I |
| V/S | 0.7619 | likely_pathogenic | 0.7357 | pathogenic | -2.514 | Highly Destabilizing | 0.555 | D | 0.751 | deleterious | None | None | None | None | I |
| V/T | 0.477 | ambiguous | 0.3945 | ambiguous | -2.171 | Highly Destabilizing | 0.149 | N | 0.688 | prob.neutral | None | None | None | None | I |
| V/W | 0.9552 | likely_pathogenic | 0.9409 | pathogenic | -1.62 | Destabilizing | 0.935 | D | 0.817 | deleterious | None | None | None | None | I |
| V/Y | 0.9015 | likely_pathogenic | 0.881 | pathogenic | -1.242 | Destabilizing | 0.555 | D | 0.759 | 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.