Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31056 | 93391;93392;93393 | chr2:178548460;178548459;178548458 | chr2:179413187;179413186;179413185 |
| N2AB | 29415 | 88468;88469;88470 | chr2:178548460;178548459;178548458 | chr2:179413187;179413186;179413185 |
| N2A | 28488 | 85687;85688;85689 | chr2:178548460;178548459;178548458 | chr2:179413187;179413186;179413185 |
| N2B | 21991 | 66196;66197;66198 | chr2:178548460;178548459;178548458 | chr2:179413187;179413186;179413185 |
| Novex-1 | 22116 | 66571;66572;66573 | chr2:178548460;178548459;178548458 | chr2:179413187;179413186;179413185 |
| Novex-2 | 22183 | 66772;66773;66774 | chr2:178548460;178548459;178548458 | chr2:179413187;179413186;179413185 |
| 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/L | None | None | 1.0 | N | 0.784 | 0.45 | 0.667105625577 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | None | None | 1.0 | N | 0.784 | 0.45 | 0.667105625577 | gnomAD-4.0.0 | 6.56668E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.93199E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs201377736  |
-1.044 | 1.0 | N | 0.685 | 0.384 | 0.231873229951 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.96335E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs201377736 |
-1.044 | 1.0 | N | 0.685 | 0.384 | 0.231873229951 | gnomAD-4.0.0 | 8.67471E-06 | None | None | None | None | N | None | 3.99808E-05 | 4.99817E-05 | None | 0 | 0 | None | 0 | 0 | 5.93318E-06 | 0 | 1.60041E-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 | 0.9863 | likely_pathogenic | 0.9826 | pathogenic | -2.364 | Highly Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| R/C | 0.7513 | likely_pathogenic | 0.7298 | pathogenic | -1.941 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| R/D | 0.9984 | likely_pathogenic | 0.9981 | pathogenic | -1.247 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| R/E | 0.98 | likely_pathogenic | 0.9741 | pathogenic | -1.022 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| R/F | 0.9876 | likely_pathogenic | 0.9872 | pathogenic | -1.466 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| R/G | 0.9708 | likely_pathogenic | 0.9636 | pathogenic | -2.68 | Highly Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.512429594 | None | None | N |
| R/H | 0.6271 | likely_pathogenic | 0.6363 | pathogenic | -2.393 | Highly Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/I | 0.9839 | likely_pathogenic | 0.979 | pathogenic | -1.42 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| R/K | 0.4 | ambiguous | 0.3612 | ambiguous | -1.231 | Destabilizing | 0.998 | D | 0.464 | neutral | None | None | None | None | N |
| R/L | 0.945 | likely_pathogenic | 0.9235 | pathogenic | -1.42 | Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.513479551 | None | None | N |
| R/M | 0.9533 | likely_pathogenic | 0.9353 | pathogenic | -1.866 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| R/N | 0.994 | likely_pathogenic | 0.9931 | pathogenic | -1.384 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.9989 | pathogenic | -1.729 | Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.550537435 | None | None | N |
| R/Q | 0.548 | ambiguous | 0.5033 | ambiguous | -1.216 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.493093891 | None | None | N |
| R/S | 0.9944 | likely_pathogenic | 0.9932 | pathogenic | -2.26 | Highly Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| R/T | 0.9904 | likely_pathogenic | 0.9867 | pathogenic | -1.833 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| R/V | 0.9822 | likely_pathogenic | 0.9782 | pathogenic | -1.729 | Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| R/W | 0.87 | likely_pathogenic | 0.8452 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| R/Y | 0.9437 | likely_pathogenic | 0.946 | pathogenic | -0.927 | Destabilizing | 1.0 | D | 0.921 | 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.