Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15133 | 45622;45623;45624 | chr2:178621321;178621320;178621319 | chr2:179486048;179486047;179486046 |
| N2AB | 13492 | 40699;40700;40701 | chr2:178621321;178621320;178621319 | chr2:179486048;179486047;179486046 |
| N2A | 12565 | 37918;37919;37920 | chr2:178621321;178621320;178621319 | chr2:179486048;179486047;179486046 |
| N2B | 6068 | 18427;18428;18429 | chr2:178621321;178621320;178621319 | chr2:179486048;179486047;179486046 |
| Novex-1 | 6193 | 18802;18803;18804 | chr2:178621321;178621320;178621319 | chr2:179486048;179486047;179486046 |
| Novex-2 | 6260 | 19003;19004;19005 | chr2:178621321;178621320;178621319 | chr2:179486048;179486047;179486046 |
| 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/D | rs781744339  |
-0.518 | 0.999 | D | 0.455 | 0.245 | 0.377274123778 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| E/D | rs781744339 |
-0.518 | 0.999 | D | 0.455 | 0.245 | 0.377274123778 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| E/D | rs781744339 |
-0.518 | 0.999 | D | 0.455 | 0.245 | 0.377274123778 | gnomAD-4.0.0 | 5.58374E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63347E-06 | 0 | 0 |
| E/Q | None | None | 1.0 | D | 0.623 | 0.371 | 0.506552580704 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.4601 | ambiguous | 0.4007 | ambiguous | -0.665 | Destabilizing | 0.999 | D | 0.612 | neutral | N | 0.440023112 | None | None | I |
| E/C | 0.9897 | likely_pathogenic | 0.9872 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| E/D | 0.7971 | likely_pathogenic | 0.7707 | pathogenic | -0.599 | Destabilizing | 0.999 | D | 0.455 | neutral | D | 0.548621855 | None | None | I |
| E/F | 0.9918 | likely_pathogenic | 0.9898 | pathogenic | -0.172 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| E/G | 0.7769 | likely_pathogenic | 0.7559 | pathogenic | -0.956 | Destabilizing | 1.0 | D | 0.615 | neutral | D | 0.640830954 | None | None | I |
| E/H | 0.9646 | likely_pathogenic | 0.9564 | pathogenic | -0.135 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| E/I | 0.8283 | likely_pathogenic | 0.7965 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| E/K | 0.6948 | likely_pathogenic | 0.6862 | pathogenic | 0.066 | Stabilizing | 0.999 | D | 0.61 | neutral | D | 0.549659249 | None | None | I |
| E/L | 0.9083 | likely_pathogenic | 0.8971 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| E/M | 0.9244 | likely_pathogenic | 0.9051 | pathogenic | 0.322 | Stabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| E/N | 0.9121 | likely_pathogenic | 0.8795 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| E/P | 0.9502 | likely_pathogenic | 0.9329 | pathogenic | -0.131 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | I |
| E/Q | 0.4612 | ambiguous | 0.4088 | ambiguous | -0.41 | Destabilizing | 1.0 | D | 0.623 | neutral | D | 0.577111324 | None | None | I |
| E/R | 0.8229 | likely_pathogenic | 0.8246 | pathogenic | 0.339 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| E/S | 0.7707 | likely_pathogenic | 0.7104 | pathogenic | -0.703 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
| E/T | 0.7902 | likely_pathogenic | 0.7504 | pathogenic | -0.453 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| E/V | 0.6487 | likely_pathogenic | 0.5978 | pathogenic | -0.131 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.438514128 | None | None | I |
| E/W | 0.998 | likely_pathogenic | 0.9978 | pathogenic | 0.119 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| E/Y | 0.9859 | likely_pathogenic | 0.9828 | pathogenic | 0.107 | Stabilizing | 1.0 | D | 0.647 | 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.