Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1705 | 5338;5339;5340 | chr2:178776751;178776750;178776749 | chr2:179641478;179641477;179641476 |
| N2AB | 1705 | 5338;5339;5340 | chr2:178776751;178776750;178776749 | chr2:179641478;179641477;179641476 |
| N2A | 1705 | 5338;5339;5340 | chr2:178776751;178776750;178776749 | chr2:179641478;179641477;179641476 |
| N2B | 1659 | 5200;5201;5202 | chr2:178776751;178776750;178776749 | chr2:179641478;179641477;179641476 |
| Novex-1 | 1659 | 5200;5201;5202 | chr2:178776751;178776750;178776749 | chr2:179641478;179641477;179641476 |
| Novex-2 | 1659 | 5200;5201;5202 | chr2:178776751;178776750;178776749 | chr2:179641478;179641477;179641476 |
| Novex-3 | 1705 | 5338;5339;5340 | chr2:178776751;178776750;178776749 | chr2:179641478;179641477;179641476 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs375828531  |
-1.943 | 0.999 | D | 0.657 | 0.809 | 0.349429436713 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs375828531 |
-1.943 | 0.999 | D | 0.657 | 0.809 | 0.349429436713 | gnomAD-4.0.0 | 1.57342E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.06837E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.997 | likely_pathogenic | 0.9977 | pathogenic | -3.36 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| F/C | 0.9901 | likely_pathogenic | 0.9942 | pathogenic | -1.991 | Destabilizing | 1.0 | D | 0.85 | deleterious | D | 0.804771404 | None | None | I |
| F/D | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -3.308 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | I |
| F/E | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -3.177 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | I |
| F/G | 0.9988 | likely_pathogenic | 0.999 | pathogenic | -3.71 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| F/H | 0.9952 | likely_pathogenic | 0.996 | pathogenic | -1.889 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| F/I | 0.9238 | likely_pathogenic | 0.9543 | pathogenic | -2.215 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.506899538 | None | None | I |
| F/K | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -1.967 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| F/L | 0.991 | likely_pathogenic | 0.9937 | pathogenic | -2.215 | Highly Destabilizing | 0.999 | D | 0.657 | neutral | D | 0.69692918 | None | None | I |
| F/M | 0.9824 | likely_pathogenic | 0.9872 | pathogenic | -1.901 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| F/N | 0.9988 | likely_pathogenic | 0.9992 | pathogenic | -2.178 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | I |
| F/P | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -2.606 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| F/Q | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -2.336 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| F/R | 0.9976 | likely_pathogenic | 0.9976 | pathogenic | -1.175 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| F/S | 0.9976 | likely_pathogenic | 0.9984 | pathogenic | -2.854 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | D | 0.804361973 | None | None | I |
| F/T | 0.998 | likely_pathogenic | 0.9985 | pathogenic | -2.634 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| F/V | 0.9547 | likely_pathogenic | 0.9701 | pathogenic | -2.606 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | D | 0.675312547 | None | None | I |
| F/W | 0.9583 | likely_pathogenic | 0.9637 | pathogenic | -0.807 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| F/Y | 0.8763 | likely_pathogenic | 0.8984 | pathogenic | -1.246 | Destabilizing | 0.999 | D | 0.645 | neutral | D | 0.804423945 | 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.