Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18983 | 57172;57173;57174 | chr2:178598763;178598762;178598761 | chr2:179463490;179463489;179463488 |
| N2AB | 17342 | 52249;52250;52251 | chr2:178598763;178598762;178598761 | chr2:179463490;179463489;179463488 |
| N2A | 16415 | 49468;49469;49470 | chr2:178598763;178598762;178598761 | chr2:179463490;179463489;179463488 |
| N2B | 9918 | 29977;29978;29979 | chr2:178598763;178598762;178598761 | chr2:179463490;179463489;179463488 |
| Novex-1 | 10043 | 30352;30353;30354 | chr2:178598763;178598762;178598761 | chr2:179463490;179463489;179463488 |
| Novex-2 | 10110 | 30553;30554;30555 | chr2:178598763;178598762;178598761 | chr2:179463490;179463489;179463488 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs377000174  |
-1.953 | 0.919 | N | 0.632 | 0.212 | None | gnomAD-2.1.1 | 9.32E-05 | None | None | None | None | N | None | 0 | 5.68E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.80616E-04 | 1.40924E-04 |
| A/T | rs377000174 |
-1.953 | 0.919 | N | 0.632 | 0.212 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17644E-04 | 0 | 9.56023E-04 |
| A/T | rs377000174 |
-1.953 | 0.919 | N | 0.632 | 0.212 | None |
Vasli (2012)
| None |
MD 
|
comp het with V1034M | None | None | N | Genetic analysis of MD patients; unknown inheritance (n = 2, 2 affected (total 3)); variant prioritisation; comp het with V1034M | None | None | None | None | None | None | None | None | None | None | None |
| A/T | rs377000174 |
-1.953 | 0.919 | N | 0.632 | 0.212 | None | gnomAD-4.0.0 | 1.0293E-04 | None | None | None | None | N | None | 1.33622E-05 | 3.34292E-05 | None | 6.76453E-05 | 0 | None | 0 | 0 | 1.33968E-04 | 0 | 4.806E-05 |
| A/V | rs774502532 |
-0.448 | 0.132 | N | 0.363 | 0.201 | 0.246215685461 | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | N | None | 0 | 2.03844E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| A/V | rs774502532 |
-0.448 | 0.132 | N | 0.363 | 0.201 | 0.246215685461 | gnomAD-4.0.0 | 1.23232E-05 | None | None | None | None | N | None | 0 | 1.79412E-04 | None | 0 | 0 | None | 0 | 0 | 7.19813E-06 | 0 | 3.3151E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5987 | likely_pathogenic | 0.6519 | pathogenic | -1.98 | Destabilizing | 0.045 | N | 0.309 | neutral | None | None | None | None | N |
| A/D | 0.9986 | likely_pathogenic | 0.9981 | pathogenic | -3.158 | Highly Destabilizing | 0.996 | D | 0.755 | deleterious | N | 0.51846262 | None | None | N |
| A/E | 0.9967 | likely_pathogenic | 0.9957 | pathogenic | -3.009 | Highly Destabilizing | 0.997 | D | 0.68 | prob.neutral | None | None | None | None | N |
| A/F | 0.9883 | likely_pathogenic | 0.9861 | pathogenic | -0.923 | Destabilizing | 0.991 | D | 0.747 | deleterious | None | None | None | None | N |
| A/G | 0.6854 | likely_pathogenic | 0.6342 | pathogenic | -1.722 | Destabilizing | 0.958 | D | 0.629 | neutral | N | 0.495750009 | None | None | N |
| A/H | 0.9972 | likely_pathogenic | 0.9969 | pathogenic | -1.728 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| A/I | 0.9124 | likely_pathogenic | 0.9059 | pathogenic | -0.44 | Destabilizing | 0.883 | D | 0.68 | prob.neutral | None | None | None | None | N |
| A/K | 0.9989 | likely_pathogenic | 0.9987 | pathogenic | -1.457 | Destabilizing | 0.997 | D | 0.683 | prob.neutral | None | None | None | None | N |
| A/L | 0.8535 | likely_pathogenic | 0.8283 | pathogenic | -0.44 | Destabilizing | 0.757 | D | 0.652 | prob.neutral | None | None | None | None | N |
| A/M | 0.93 | likely_pathogenic | 0.9201 | pathogenic | -0.962 | Destabilizing | 0.991 | D | 0.692 | prob.delet. | None | None | None | None | N |
| A/N | 0.9915 | likely_pathogenic | 0.9903 | pathogenic | -1.863 | Destabilizing | 0.997 | D | 0.747 | deleterious | None | None | None | None | N |
| A/P | 0.8495 | likely_pathogenic | 0.8749 | pathogenic | -0.714 | Destabilizing | 0.996 | D | 0.727 | deleterious | N | 0.49782347 | None | None | N |
| A/Q | 0.9903 | likely_pathogenic | 0.9888 | pathogenic | -1.798 | Destabilizing | 0.997 | D | 0.69 | prob.delet. | None | None | None | None | N |
| A/R | 0.9938 | likely_pathogenic | 0.9925 | pathogenic | -1.356 | Destabilizing | 0.997 | D | 0.717 | prob.delet. | None | None | None | None | N |
| A/S | 0.4481 | ambiguous | 0.4475 | ambiguous | -2.133 | Highly Destabilizing | 0.958 | D | 0.635 | neutral | N | 0.517702151 | None | None | N |
| A/T | 0.7957 | likely_pathogenic | 0.7537 | pathogenic | -1.889 | Destabilizing | 0.919 | D | 0.632 | neutral | N | 0.477948469 | None | None | N |
| A/V | 0.6923 | likely_pathogenic | 0.6811 | pathogenic | -0.714 | Destabilizing | 0.132 | N | 0.363 | neutral | N | 0.462642144 | None | None | N |
| A/W | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -1.512 | Destabilizing | 0.999 | D | 0.774 | deleterious | None | None | None | None | N |
| A/Y | 0.9966 | likely_pathogenic | 0.996 | pathogenic | -1.096 | Destabilizing | 0.997 | D | 0.747 | 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.