Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18218 | 54877;54878;54879 | chr2:178604035;178604034;178604033 | chr2:179468762;179468761;179468760 |
| N2AB | 16577 | 49954;49955;49956 | chr2:178604035;178604034;178604033 | chr2:179468762;179468761;179468760 |
| N2A | 15650 | 47173;47174;47175 | chr2:178604035;178604034;178604033 | chr2:179468762;179468761;179468760 |
| N2B | 9153 | 27682;27683;27684 | chr2:178604035;178604034;178604033 | chr2:179468762;179468761;179468760 |
| Novex-1 | 9278 | 28057;28058;28059 | chr2:178604035;178604034;178604033 | chr2:179468762;179468761;179468760 |
| Novex-2 | 9345 | 28258;28259;28260 | chr2:178604035;178604034;178604033 | chr2:179468762;179468761;179468760 |
| 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/Q | rs143643360  |
0.171 | 0.993 | N | 0.601 | 0.31 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 0 |
| R/Q | rs143643360 |
0.171 | 0.993 | N | 0.601 | 0.31 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| R/Q | rs143643360 |
0.171 | 0.993 | N | 0.601 | 0.31 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs143643360 |
0.171 | 0.993 | N | 0.601 | 0.31 | None | gnomAD-4.0.0 | 2.728E-05 | None | None | None | None | I | None | 4.0032E-05 | 0 | None | 0 | 0 | None | 3.12422E-05 | 1.65344E-04 | 3.22252E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8993 | likely_pathogenic | 0.8611 | pathogenic | -0.141 | Destabilizing | 0.931 | D | 0.536 | neutral | None | None | None | None | I |
| R/C | 0.8149 | likely_pathogenic | 0.7506 | pathogenic | -0.493 | Destabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | I |
| R/D | 0.962 | likely_pathogenic | 0.9551 | pathogenic | -0.486 | Destabilizing | 0.996 | D | 0.557 | neutral | None | None | None | None | I |
| R/E | 0.9052 | likely_pathogenic | 0.8693 | pathogenic | -0.469 | Destabilizing | 0.97 | D | 0.556 | neutral | None | None | None | None | I |
| R/F | 0.9438 | likely_pathogenic | 0.9217 | pathogenic | -0.515 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | I |
| R/G | 0.8358 | likely_pathogenic | 0.7733 | pathogenic | -0.226 | Destabilizing | 0.992 | D | 0.554 | neutral | N | 0.510390541 | None | None | I |
| R/H | 0.5222 | ambiguous | 0.3936 | ambiguous | -0.668 | Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | I |
| R/I | 0.8738 | likely_pathogenic | 0.8162 | pathogenic | 0.036 | Stabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | I |
| R/K | 0.3112 | likely_benign | 0.2483 | benign | -0.469 | Destabilizing | 0.155 | N | 0.202 | neutral | None | None | None | None | I |
| R/L | 0.7927 | likely_pathogenic | 0.7035 | pathogenic | 0.036 | Stabilizing | 0.992 | D | 0.554 | neutral | N | 0.494306368 | None | None | I |
| R/M | 0.8861 | likely_pathogenic | 0.8298 | pathogenic | -0.305 | Destabilizing | 1.0 | D | 0.58 | neutral | None | None | None | None | I |
| R/N | 0.947 | likely_pathogenic | 0.9323 | pathogenic | -0.428 | Destabilizing | 0.985 | D | 0.577 | neutral | None | None | None | None | I |
| R/P | 0.8788 | likely_pathogenic | 0.8335 | pathogenic | -0.009 | Destabilizing | 0.999 | D | 0.588 | neutral | N | 0.493228933 | None | None | I |
| R/Q | 0.4992 | ambiguous | 0.3699 | ambiguous | -0.428 | Destabilizing | 0.993 | D | 0.601 | neutral | N | 0.492919501 | None | None | I |
| R/S | 0.9382 | likely_pathogenic | 0.9088 | pathogenic | -0.533 | Destabilizing | 0.97 | D | 0.57 | neutral | None | None | None | None | I |
| R/T | 0.8714 | likely_pathogenic | 0.8051 | pathogenic | -0.438 | Destabilizing | 0.985 | D | 0.577 | neutral | None | None | None | None | I |
| R/V | 0.887 | likely_pathogenic | 0.8324 | pathogenic | -0.009 | Destabilizing | 0.996 | D | 0.575 | neutral | None | None | None | None | I |
| R/W | 0.707 | likely_pathogenic | 0.5774 | pathogenic | -0.747 | Destabilizing | 1.0 | D | 0.624 | neutral | None | None | None | None | I |
| R/Y | 0.8683 | likely_pathogenic | 0.8133 | pathogenic | -0.386 | Destabilizing | 0.999 | D | 0.582 | neutral | 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.