Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20494 | 61705;61706;61707 | chr2:178590245;178590244;178590243 | chr2:179454972;179454971;179454970 |
| N2AB | 18853 | 56782;56783;56784 | chr2:178590245;178590244;178590243 | chr2:179454972;179454971;179454970 |
| N2A | 17926 | 54001;54002;54003 | chr2:178590245;178590244;178590243 | chr2:179454972;179454971;179454970 |
| N2B | 11429 | 34510;34511;34512 | chr2:178590245;178590244;178590243 | chr2:179454972;179454971;179454970 |
| Novex-1 | 11554 | 34885;34886;34887 | chr2:178590245;178590244;178590243 | chr2:179454972;179454971;179454970 |
| Novex-2 | 11621 | 35086;35087;35088 | chr2:178590245;178590244;178590243 | chr2:179454972;179454971;179454970 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.889 | N | 0.362 | 0.133 | 0.461323234107 | gnomAD-4.0.0 | 6.97205E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53691E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs374845737  |
-2.45 | 0.989 | N | 0.708 | 0.42 | None | gnomAD-2.1.1 | 2.21E-05 | None | None | None | None | N | None | 3.28861E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs374845737 |
-2.45 | 0.989 | N | 0.708 | 0.42 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.44851E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs374845737 |
-2.45 | 0.989 | N | 0.708 | 0.42 | None | gnomAD-4.0.0 | 1.58831E-05 | None | None | None | None | N | None | 1.88343E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.93496E-05 |
| I/V | None | None | 0.333 | N | 0.19 | 0.073 | 0.329282125956 | gnomAD-4.0.0 | 1.39441E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.82057E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9318 | likely_pathogenic | 0.9549 | pathogenic | -2.76 | Highly Destabilizing | 0.992 | D | 0.567 | neutral | None | None | None | None | N |
| I/C | 0.9445 | likely_pathogenic | 0.9607 | pathogenic | -1.992 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/D | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -3.218 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| I/E | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -2.965 | Highly Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| I/F | 0.5213 | ambiguous | 0.6257 | pathogenic | -1.68 | Destabilizing | 0.998 | D | 0.707 | prob.neutral | N | 0.513813983 | None | None | N |
| I/G | 0.9948 | likely_pathogenic | 0.9964 | pathogenic | -3.328 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| I/H | 0.9957 | likely_pathogenic | 0.9965 | pathogenic | -2.687 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| I/K | 0.9956 | likely_pathogenic | 0.9958 | pathogenic | -2.333 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/L | 0.2159 | likely_benign | 0.2521 | benign | -1.099 | Destabilizing | 0.889 | D | 0.362 | neutral | N | 0.461131504 | None | None | N |
| I/M | 0.3157 | likely_benign | 0.3743 | ambiguous | -0.966 | Destabilizing | 0.998 | D | 0.68 | prob.neutral | N | 0.512987263 | None | None | N |
| I/N | 0.9911 | likely_pathogenic | 0.9918 | pathogenic | -2.763 | Highly Destabilizing | 0.999 | D | 0.807 | deleterious | N | 0.500841074 | None | None | N |
| I/P | 0.9965 | likely_pathogenic | 0.9964 | pathogenic | -1.636 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| I/Q | 0.9952 | likely_pathogenic | 0.9955 | pathogenic | -2.6 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/R | 0.993 | likely_pathogenic | 0.9932 | pathogenic | -2.018 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| I/S | 0.9821 | likely_pathogenic | 0.9861 | pathogenic | -3.444 | Highly Destabilizing | 0.998 | D | 0.763 | deleterious | N | 0.482483329 | None | None | N |
| I/T | 0.966 | likely_pathogenic | 0.977 | pathogenic | -3.035 | Highly Destabilizing | 0.989 | D | 0.708 | prob.delet. | N | 0.456630393 | None | None | N |
| I/V | 0.1305 | likely_benign | 0.1627 | benign | -1.636 | Destabilizing | 0.333 | N | 0.19 | neutral | N | 0.426016066 | None | None | N |
| I/W | 0.9928 | likely_pathogenic | 0.9949 | pathogenic | -2.066 | Highly Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| I/Y | 0.9702 | likely_pathogenic | 0.9768 | pathogenic | -1.788 | Destabilizing | 1.0 | D | 0.755 | deleterious | 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.