Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35986 | 108181;108182;108183 | chr2:178527032;178527031;178527030 | chr2:179391759;179391758;179391757 |
| N2AB | 34345 | 103258;103259;103260 | chr2:178527032;178527031;178527030 | chr2:179391759;179391758;179391757 |
| N2A | 33418 | 100477;100478;100479 | chr2:178527032;178527031;178527030 | chr2:179391759;179391758;179391757 |
| N2B | 26921 | 80986;80987;80988 | chr2:178527032;178527031;178527030 | chr2:179391759;179391758;179391757 |
| Novex-1 | 27046 | 81361;81362;81363 | chr2:178527032;178527031;178527030 | chr2:179391759;179391758;179391757 |
| Novex-2 | 27113 | 81562;81563;81564 | chr2:178527032;178527031;178527030 | chr2:179391759;179391758;179391757 |
| 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/M | None | None | 0.997 | N | 0.717 | 0.319 | 0.44750879378 | gnomAD-4.0.0 | 6.84448E-07 | None | None | None | -1.243(OBSL1) -1.08(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99656E-07 | 0 | 0 |
| I/T | rs1060500541  |
-3.068 | 0.978 | N | 0.752 | 0.445 | 0.636217269286 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | -0.777(OBSL1) -0.537(OBSCN) | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1060500541 |
-3.068 | 0.978 | N | 0.752 | 0.445 | 0.636217269286 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | -0.777(OBSL1) -0.537(OBSCN) | N | None | 0 | 4.47467E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9848 | likely_pathogenic | 0.9862 | pathogenic | -2.815 | Highly Destabilizing | 0.983 | D | 0.695 | prob.neutral | None | None | None | -0.341(OBSL1) -0.335(OBSCN) | N |
| I/C | 0.9754 | likely_pathogenic | 0.9789 | pathogenic | -2.157 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | -1.398(OBSL1) -1.079(OBSCN) | N |
| I/D | 0.9987 | likely_pathogenic | 0.9985 | pathogenic | -3.219 | Highly Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | -0.889(OBSL1) -0.68(OBSCN) | N |
| I/E | 0.9976 | likely_pathogenic | 0.9971 | pathogenic | -3.007 | Highly Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | -1.075(OBSL1) -0.858(OBSCN) | N |
| I/F | 0.6426 | likely_pathogenic | 0.6493 | pathogenic | -1.784 | Destabilizing | 0.998 | D | 0.741 | deleterious | None | None | None | -1.105(OBSL1) -0.986(OBSCN) | N |
| I/G | 0.9967 | likely_pathogenic | 0.9967 | pathogenic | -3.362 | Highly Destabilizing | 0.999 | D | 0.853 | deleterious | None | None | None | -0.206(OBSL1) -0.197(OBSCN) | N |
| I/H | 0.9934 | likely_pathogenic | 0.9926 | pathogenic | -2.754 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | -0.453(OBSL1) -0.188(OBSCN) | N |
| I/K | 0.9911 | likely_pathogenic | 0.9892 | pathogenic | -2.22 | Highly Destabilizing | 0.999 | D | 0.862 | deleterious | N | 0.477736843 | None | -1.365(OBSL1) -1.056(OBSCN) | N |
| I/L | 0.3497 | ambiguous | 0.3545 | ambiguous | -1.229 | Destabilizing | 0.798 | D | 0.475 | neutral | N | 0.385712947 | None | -0.826(OBSL1) -0.813(OBSCN) | N |
| I/M | 0.4855 | ambiguous | 0.5115 | ambiguous | -1.119 | Destabilizing | 0.997 | D | 0.717 | prob.delet. | N | 0.465620069 | None | -1.243(OBSL1) -1.08(OBSCN) | N |
| I/N | 0.9762 | likely_pathogenic | 0.9738 | pathogenic | -2.557 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | -0.838(OBSL1) -0.671(OBSCN) | N |
| I/P | 0.9978 | likely_pathogenic | 0.9974 | pathogenic | -1.74 | Destabilizing | 0.999 | D | 0.855 | deleterious | None | None | None | -0.652(OBSL1) -0.645(OBSCN) | N |
| I/Q | 0.9941 | likely_pathogenic | 0.9932 | pathogenic | -2.456 | Highly Destabilizing | 0.999 | D | 0.852 | deleterious | None | None | None | -0.989(OBSL1) -0.792(OBSCN) | N |
| I/R | 0.9858 | likely_pathogenic | 0.983 | pathogenic | -1.818 | Destabilizing | 0.999 | D | 0.852 | deleterious | N | 0.477736843 | None | -1.434(OBSL1) -1.081(OBSCN) | N |
| I/S | 0.9831 | likely_pathogenic | 0.9826 | pathogenic | -3.261 | Highly Destabilizing | 0.998 | D | 0.828 | deleterious | None | None | None | -0.569(OBSL1) -0.335(OBSCN) | N |
| I/T | 0.9746 | likely_pathogenic | 0.9758 | pathogenic | -2.904 | Highly Destabilizing | 0.978 | D | 0.752 | deleterious | N | 0.477736843 | None | -0.777(OBSL1) -0.537(OBSCN) | N |
| I/V | 0.2736 | likely_benign | 0.2979 | benign | -1.74 | Destabilizing | 0.198 | N | 0.225 | neutral | N | 0.367738553 | None | -0.652(OBSL1) -0.645(OBSCN) | N |
| I/W | 0.9921 | likely_pathogenic | 0.9924 | pathogenic | -2.186 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | -1.633(OBSL1) -1.429(OBSCN) | N |
| I/Y | 0.9542 | likely_pathogenic | 0.9526 | pathogenic | -1.939 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | -1.168(OBSL1) -1.049(OBSCN) | 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.