Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17718 | 53377;53378;53379 | chr2:178607536;178607535;178607534 | chr2:179472263;179472262;179472261 |
| N2AB | 16077 | 48454;48455;48456 | chr2:178607536;178607535;178607534 | chr2:179472263;179472262;179472261 |
| N2A | 15150 | 45673;45674;45675 | chr2:178607536;178607535;178607534 | chr2:179472263;179472262;179472261 |
| N2B | 8653 | 26182;26183;26184 | chr2:178607536;178607535;178607534 | chr2:179472263;179472262;179472261 |
| Novex-1 | 8778 | 26557;26558;26559 | chr2:178607536;178607535;178607534 | chr2:179472263;179472262;179472261 |
| Novex-2 | 8845 | 26758;26759;26760 | chr2:178607536;178607535;178607534 | chr2:179472263;179472262;179472261 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs757223139  |
-1.367 | 0.968 | N | 0.732 | 0.372 | 0.71530076483 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs757223139 |
-1.367 | 0.968 | N | 0.732 | 0.372 | 0.71530076483 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77331E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | None | None | 0.811 | D | 0.702 | 0.437 | 0.781884890362 | gnomAD-4.0.0 | 2.05322E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69919E-06 | 0 | 0 |
| V/I | rs757223139 |
-0.586 | 0.64 | N | 0.579 | 0.238 | 0.491523185611 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs757223139 |
-0.586 | 0.64 | N | 0.579 | 0.238 | 0.491523185611 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs757223139 |
-0.586 | 0.64 | N | 0.579 | 0.238 | 0.491523185611 | gnomAD-4.0.0 | 6.57929E-06 | None | None | None | None | N | None | 0 | 6.55566E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.218 | likely_benign | 0.2412 | benign | -1.665 | Destabilizing | 0.011 | N | 0.248 | neutral | N | 0.472704519 | None | None | N |
| V/C | 0.7644 | likely_pathogenic | 0.7813 | pathogenic | -1.22 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/D | 0.8589 | likely_pathogenic | 0.8985 | pathogenic | -1.899 | Destabilizing | 0.984 | D | 0.791 | deleterious | N | 0.494788272 | None | None | N |
| V/E | 0.7432 | likely_pathogenic | 0.8098 | pathogenic | -1.792 | Destabilizing | 0.976 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/F | 0.3551 | ambiguous | 0.3931 | ambiguous | -1.085 | Destabilizing | 0.968 | D | 0.732 | prob.delet. | N | 0.482092006 | None | None | N |
| V/G | 0.4098 | ambiguous | 0.4943 | ambiguous | -2.093 | Highly Destabilizing | 0.811 | D | 0.702 | prob.neutral | D | 0.528443158 | None | None | N |
| V/H | 0.9031 | likely_pathogenic | 0.93 | pathogenic | -1.796 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| V/I | 0.1038 | likely_benign | 0.0999 | benign | -0.54 | Destabilizing | 0.64 | D | 0.579 | neutral | N | 0.439263949 | None | None | N |
| V/K | 0.8325 | likely_pathogenic | 0.8785 | pathogenic | -1.645 | Destabilizing | 0.976 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/L | 0.4189 | ambiguous | 0.4329 | ambiguous | -0.54 | Destabilizing | 0.64 | D | 0.511 | neutral | N | 0.504275432 | None | None | N |
| V/M | 0.2479 | likely_benign | 0.2747 | benign | -0.456 | Destabilizing | 0.702 | D | 0.475 | neutral | None | None | None | None | N |
| V/N | 0.7636 | likely_pathogenic | 0.817 | pathogenic | -1.661 | Destabilizing | 0.988 | D | 0.798 | deleterious | None | None | None | None | N |
| V/P | 0.9496 | likely_pathogenic | 0.9622 | pathogenic | -0.882 | Destabilizing | 0.988 | D | 0.749 | deleterious | None | None | None | None | N |
| V/Q | 0.7611 | likely_pathogenic | 0.8204 | pathogenic | -1.656 | Destabilizing | 0.988 | D | 0.746 | deleterious | None | None | None | None | N |
| V/R | 0.7886 | likely_pathogenic | 0.8393 | pathogenic | -1.275 | Destabilizing | 0.988 | D | 0.799 | deleterious | None | None | None | None | N |
| V/S | 0.4629 | ambiguous | 0.5335 | ambiguous | -2.2 | Highly Destabilizing | 0.851 | D | 0.669 | neutral | None | None | None | None | N |
| V/T | 0.2687 | likely_benign | 0.3163 | benign | -1.964 | Destabilizing | 0.919 | D | 0.552 | neutral | None | None | None | None | N |
| V/W | 0.9426 | likely_pathogenic | 0.9536 | pathogenic | -1.48 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| V/Y | 0.7724 | likely_pathogenic | 0.8047 | pathogenic | -1.118 | Destabilizing | 0.996 | D | 0.721 | prob.delet. | 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.