Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24615 | 74068;74069;74070 | chr2:178572289;178572288;178572287 | chr2:179437016;179437015;179437014 |
| N2AB | 22974 | 69145;69146;69147 | chr2:178572289;178572288;178572287 | chr2:179437016;179437015;179437014 |
| N2A | 22047 | 66364;66365;66366 | chr2:178572289;178572288;178572287 | chr2:179437016;179437015;179437014 |
| N2B | 15550 | 46873;46874;46875 | chr2:178572289;178572288;178572287 | chr2:179437016;179437015;179437014 |
| Novex-1 | 15675 | 47248;47249;47250 | chr2:178572289;178572288;178572287 | chr2:179437016;179437015;179437014 |
| Novex-2 | 15742 | 47449;47450;47451 | chr2:178572289;178572288;178572287 | chr2:179437016;179437015;179437014 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs374131909  |
0.223 | 0.996 | N | 0.786 | 0.372 | 0.441844919209 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| E/K | rs374131909 |
0.223 | 0.996 | N | 0.786 | 0.372 | 0.441844919209 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| E/K | rs374131909 |
0.223 | 0.996 | N | 0.786 | 0.372 | 0.441844919209 | gnomAD-4.0.0 | 6.57557E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47054E-05 | 0 | 0 |
| E/Q | rs374131909 |
0.088 | 0.998 | N | 0.662 | 0.275 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66389E-04 |
| E/Q | rs374131909 |
0.088 | 0.998 | N | 0.662 | 0.275 | None | gnomAD-4.0.0 | 1.36952E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80033E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.6874 | likely_pathogenic | 0.6627 | pathogenic | -0.022 | Destabilizing | 0.993 | D | 0.776 | deleterious | N | 0.514934277 | None | None | N |
| E/C | 0.979 | likely_pathogenic | 0.9807 | pathogenic | -0.096 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| E/D | 0.5566 | ambiguous | 0.4651 | ambiguous | -0.244 | Destabilizing | 0.946 | D | 0.65 | prob.neutral | N | 0.480688418 | None | None | N |
| E/F | 0.9914 | likely_pathogenic | 0.9901 | pathogenic | -0.066 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| E/G | 0.7157 | likely_pathogenic | 0.6952 | pathogenic | -0.141 | Destabilizing | 0.999 | D | 0.661 | prob.neutral | N | 0.461841996 | None | None | N |
| E/H | 0.9664 | likely_pathogenic | 0.9642 | pathogenic | 0.462 | Stabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| E/I | 0.9569 | likely_pathogenic | 0.9495 | pathogenic | 0.232 | Stabilizing | 0.998 | D | 0.706 | prob.delet. | None | None | None | None | N |
| E/K | 0.8374 | likely_pathogenic | 0.8375 | pathogenic | 0.472 | Stabilizing | 0.996 | D | 0.786 | deleterious | N | 0.485924186 | None | None | N |
| E/L | 0.9516 | likely_pathogenic | 0.9451 | pathogenic | 0.232 | Stabilizing | 0.998 | D | 0.686 | prob.delet. | None | None | None | None | N |
| E/M | 0.9311 | likely_pathogenic | 0.9214 | pathogenic | 0.062 | Stabilizing | 0.997 | D | 0.783 | deleterious | None | None | None | None | N |
| E/N | 0.8754 | likely_pathogenic | 0.8559 | pathogenic | 0.252 | Stabilizing | 0.996 | D | 0.771 | deleterious | None | None | None | None | N |
| E/P | 0.9972 | likely_pathogenic | 0.9965 | pathogenic | 0.166 | Stabilizing | 0.988 | D | 0.691 | prob.delet. | None | None | None | None | N |
| E/Q | 0.4043 | ambiguous | 0.4111 | ambiguous | 0.262 | Stabilizing | 0.998 | D | 0.662 | prob.neutral | N | 0.46617409 | None | None | N |
| E/R | 0.8997 | likely_pathogenic | 0.9009 | pathogenic | 0.66 | Stabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | N |
| E/S | 0.717 | likely_pathogenic | 0.6892 | pathogenic | 0.108 | Stabilizing | 0.994 | D | 0.767 | deleterious | None | None | None | None | N |
| E/T | 0.8672 | likely_pathogenic | 0.8572 | pathogenic | 0.213 | Stabilizing | 0.999 | D | 0.733 | deleterious | None | None | None | None | N |
| E/V | 0.8599 | likely_pathogenic | 0.8501 | pathogenic | 0.166 | Stabilizing | 0.997 | D | 0.695 | prob.delet. | N | 0.488797795 | None | None | N |
| E/W | 0.998 | likely_pathogenic | 0.9976 | pathogenic | -0.018 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| E/Y | 0.9875 | likely_pathogenic | 0.9855 | pathogenic | 0.16 | Stabilizing | 1.0 | D | 0.73 | 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.