Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4811 | 14656;14657;14658 | chr2:178736015;178736014;178736013 | chr2:179600742;179600741;179600740 |
| N2AB | 4494 | 13705;13706;13707 | chr2:178736015;178736014;178736013 | chr2:179600742;179600741;179600740 |
| N2A | 3567 | 10924;10925;10926 | chr2:178736015;178736014;178736013 | chr2:179600742;179600741;179600740 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs761096621  |
None | None | N | 0.113 | 0.145 | 0.0551355673512 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/S | rs761096621 |
None | None | N | 0.113 | 0.145 | 0.0551355673512 | gnomAD-4.0.0 | 6.57186E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46994E-05 | 0 | 0 |
| A/T | rs761096621 |
-0.74 | None | N | 0.136 | 0.206 | 0.0611884634855 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 0 |
| A/T | rs761096621 |
-0.74 | None | N | 0.136 | 0.206 | 0.0611884634855 | gnomAD-4.0.0 | 2.74008E-06 | None | None | None | None | I | None | 2.9924E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.48667E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5325 | ambiguous | 0.5308 | ambiguous | -0.789 | Destabilizing | 0.676 | D | 0.367 | neutral | None | None | None | None | I |
| A/D | 0.2203 | likely_benign | 0.2484 | benign | -0.422 | Destabilizing | 0.038 | N | 0.37 | neutral | None | None | None | None | I |
| A/E | 0.187 | likely_benign | 0.2012 | benign | -0.532 | Destabilizing | 0.001 | N | 0.196 | neutral | N | 0.431552909 | None | None | I |
| A/F | 0.3185 | likely_benign | 0.34 | benign | -0.85 | Destabilizing | 0.356 | N | 0.418 | neutral | None | None | None | None | I |
| A/G | 0.1397 | likely_benign | 0.1358 | benign | -0.615 | Destabilizing | 0.012 | N | 0.228 | neutral | N | 0.448052847 | None | None | I |
| A/H | 0.4057 | ambiguous | 0.3998 | ambiguous | -0.645 | Destabilizing | 0.356 | N | 0.401 | neutral | None | None | None | None | I |
| A/I | 0.2328 | likely_benign | 0.2262 | benign | -0.274 | Destabilizing | 0.038 | N | 0.421 | neutral | None | None | None | None | I |
| A/K | 0.3032 | likely_benign | 0.3135 | benign | -0.799 | Destabilizing | None | N | 0.196 | neutral | None | None | None | None | I |
| A/L | 0.1816 | likely_benign | 0.1726 | benign | -0.274 | Destabilizing | 0.016 | N | 0.344 | neutral | None | None | None | None | I |
| A/M | 0.1936 | likely_benign | 0.1849 | benign | -0.331 | Destabilizing | 0.356 | N | 0.38 | neutral | None | None | None | None | I |
| A/N | 0.1921 | likely_benign | 0.1865 | benign | -0.456 | Destabilizing | None | N | 0.241 | neutral | None | None | None | None | I |
| A/P | 0.1683 | likely_benign | 0.1603 | benign | -0.302 | Destabilizing | None | N | 0.196 | neutral | N | 0.417567855 | None | None | I |
| A/Q | 0.2783 | likely_benign | 0.2674 | benign | -0.682 | Destabilizing | 0.003 | N | 0.217 | neutral | None | None | None | None | I |
| A/R | 0.2941 | likely_benign | 0.3085 | benign | -0.381 | Destabilizing | None | N | 0.197 | neutral | None | None | None | None | I |
| A/S | 0.0945 | likely_benign | 0.0906 | benign | -0.761 | Destabilizing | None | N | 0.113 | neutral | N | 0.385035624 | None | None | I |
| A/T | 0.0766 | likely_benign | 0.0738 | benign | -0.775 | Destabilizing | None | N | 0.136 | neutral | N | 0.352575791 | None | None | I |
| A/V | 0.1229 | likely_benign | 0.1227 | benign | -0.302 | Destabilizing | None | N | 0.166 | neutral | N | 0.349772382 | None | None | I |
| A/W | 0.6811 | likely_pathogenic | 0.7144 | pathogenic | -1.047 | Destabilizing | 0.864 | D | 0.439 | neutral | None | None | None | None | I |
| A/Y | 0.4051 | ambiguous | 0.4326 | ambiguous | -0.674 | Destabilizing | 0.356 | N | 0.417 | neutral | 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.