Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20569 | 61930;61931;61932 | chr2:178590020;178590019;178590018 | chr2:179454747;179454746;179454745 |
| N2AB | 18928 | 57007;57008;57009 | chr2:178590020;178590019;178590018 | chr2:179454747;179454746;179454745 |
| N2A | 18001 | 54226;54227;54228 | chr2:178590020;178590019;178590018 | chr2:179454747;179454746;179454745 |
| N2B | 11504 | 34735;34736;34737 | chr2:178590020;178590019;178590018 | chr2:179454747;179454746;179454745 |
| Novex-1 | 11629 | 35110;35111;35112 | chr2:178590020;178590019;178590018 | chr2:179454747;179454746;179454745 |
| Novex-2 | 11696 | 35311;35312;35313 | chr2:178590020;178590019;178590018 | chr2:179454747;179454746;179454745 |
| 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/K | rs371014957  |
-0.675 | 0.994 | N | 0.537 | 0.295 | None | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/K | rs371014957 |
-0.675 | 0.994 | N | 0.537 | 0.295 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/K | rs371014957 |
-0.675 | 0.994 | N | 0.537 | 0.295 | None | gnomAD-4.0.0 | 3.78162E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08695E-05 | 0 | 1.60174E-05 |
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 | 0.7742 | likely_pathogenic | 0.7313 | pathogenic | -0.195 | Destabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | I |
| R/C | 0.3533 | ambiguous | 0.3217 | benign | -0.269 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | I |
| R/D | 0.9679 | likely_pathogenic | 0.9598 | pathogenic | -0.02 | Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | I |
| R/E | 0.8111 | likely_pathogenic | 0.7689 | pathogenic | 0.068 | Stabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/F | 0.8607 | likely_pathogenic | 0.8354 | pathogenic | -0.263 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| R/G | 0.7946 | likely_pathogenic | 0.7809 | pathogenic | -0.439 | Destabilizing | 0.999 | D | 0.705 | prob.delet. | N | 0.477924199 | None | None | I |
| R/H | 0.2998 | likely_benign | 0.3054 | benign | -0.876 | Destabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | I |
| R/I | 0.413 | ambiguous | 0.3419 | ambiguous | 0.428 | Stabilizing | 0.999 | D | 0.845 | deleterious | N | 0.469311057 | None | None | I |
| R/K | 0.2062 | likely_benign | 0.1936 | benign | -0.264 | Destabilizing | 0.994 | D | 0.537 | neutral | N | 0.420613033 | None | None | I |
| R/L | 0.5103 | ambiguous | 0.4913 | ambiguous | 0.428 | Stabilizing | 0.999 | D | 0.705 | prob.delet. | None | None | None | None | I |
| R/M | 0.5993 | likely_pathogenic | 0.553 | ambiguous | None | Stabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| R/N | 0.8946 | likely_pathogenic | 0.8779 | pathogenic | 0.073 | Stabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | I |
| R/P | 0.8988 | likely_pathogenic | 0.8686 | pathogenic | 0.242 | Stabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | I |
| R/Q | 0.2578 | likely_benign | 0.2421 | benign | -0.049 | Destabilizing | 0.999 | D | 0.794 | deleterious | None | None | None | None | I |
| R/S | 0.8268 | likely_pathogenic | 0.8044 | pathogenic | -0.411 | Destabilizing | 0.999 | D | 0.768 | deleterious | N | 0.509253525 | None | None | I |
| R/T | 0.4985 | ambiguous | 0.4756 | ambiguous | -0.168 | Destabilizing | 0.999 | D | 0.762 | deleterious | N | 0.480893488 | None | None | I |
| R/V | 0.5184 | ambiguous | 0.445 | ambiguous | 0.242 | Stabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | I |
| R/W | 0.5943 | likely_pathogenic | 0.5971 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| R/Y | 0.7553 | likely_pathogenic | 0.7338 | pathogenic | 0.19 | Stabilizing | 0.999 | D | 0.881 | 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.