Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32238 | 96937;96938;96939 | chr2:178543261;178543260;178543259 | chr2:179407988;179407987;179407986 |
| N2AB | 30597 | 92014;92015;92016 | chr2:178543261;178543260;178543259 | chr2:179407988;179407987;179407986 |
| N2A | 29670 | 89233;89234;89235 | chr2:178543261;178543260;178543259 | chr2:179407988;179407987;179407986 |
| N2B | 23173 | 69742;69743;69744 | chr2:178543261;178543260;178543259 | chr2:179407988;179407987;179407986 |
| Novex-1 | 23298 | 70117;70118;70119 | chr2:178543261;178543260;178543259 | chr2:179407988;179407987;179407986 |
| Novex-2 | 23365 | 70318;70319;70320 | chr2:178543261;178543260;178543259 | chr2:179407988;179407987;179407986 |
| 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/A | None | None | 0.822 | N | 0.665 | 0.234 | 0.610312411291 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/L | rs758769330  |
-0.387 | 0.014 | N | 0.434 | 0.106 | 0.435262743402 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| V/L | rs758769330 |
-0.387 | 0.014 | N | 0.434 | 0.106 | 0.435262743402 | gnomAD-4.0.0 | 1.59113E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85812E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3834 | ambiguous | 0.3455 | ambiguous | -2.332 | Highly Destabilizing | 0.822 | D | 0.665 | neutral | N | 0.471088842 | None | None | N |
| V/C | 0.7456 | likely_pathogenic | 0.7072 | pathogenic | -1.826 | Destabilizing | 0.998 | D | 0.732 | prob.delet. | None | None | None | None | N |
| V/D | 0.5978 | likely_pathogenic | 0.5758 | pathogenic | -3.003 | Highly Destabilizing | 0.99 | D | 0.817 | deleterious | N | 0.472316609 | None | None | N |
| V/E | 0.4301 | ambiguous | 0.4081 | ambiguous | -2.819 | Highly Destabilizing | 0.993 | D | 0.727 | prob.delet. | None | None | None | None | N |
| V/F | 0.2184 | likely_benign | 0.1876 | benign | -1.38 | Destabilizing | 0.942 | D | 0.717 | prob.delet. | N | 0.510707467 | None | None | N |
| V/G | 0.4709 | ambiguous | 0.4481 | ambiguous | -2.812 | Highly Destabilizing | 0.971 | D | 0.785 | deleterious | N | 0.486675109 | None | None | N |
| V/H | 0.6468 | likely_pathogenic | 0.6114 | pathogenic | -2.423 | Highly Destabilizing | 0.998 | D | 0.791 | deleterious | None | None | None | None | N |
| V/I | 0.0767 | likely_benign | 0.07 | benign | -0.994 | Destabilizing | 0.014 | N | 0.309 | neutral | N | 0.430265171 | None | None | N |
| V/K | 0.646 | likely_pathogenic | 0.6103 | pathogenic | -2.011 | Highly Destabilizing | 0.978 | D | 0.727 | prob.delet. | None | None | None | None | N |
| V/L | 0.1753 | likely_benign | 0.1432 | benign | -0.994 | Destabilizing | 0.014 | N | 0.434 | neutral | N | 0.495025939 | None | None | N |
| V/M | 0.1742 | likely_benign | 0.142 | benign | -1.043 | Destabilizing | 0.956 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/N | 0.4677 | ambiguous | 0.407 | ambiguous | -2.258 | Highly Destabilizing | 0.993 | D | 0.822 | deleterious | None | None | None | None | N |
| V/P | 0.9763 | likely_pathogenic | 0.9759 | pathogenic | -1.415 | Destabilizing | 0.993 | D | 0.752 | deleterious | None | None | None | None | N |
| V/Q | 0.4622 | ambiguous | 0.4325 | ambiguous | -2.172 | Highly Destabilizing | 0.993 | D | 0.759 | deleterious | None | None | None | None | N |
| V/R | 0.5444 | ambiguous | 0.5384 | ambiguous | -1.67 | Destabilizing | 0.978 | D | 0.822 | deleterious | None | None | None | None | N |
| V/S | 0.3761 | ambiguous | 0.341 | ambiguous | -2.822 | Highly Destabilizing | 0.978 | D | 0.7 | prob.neutral | None | None | None | None | N |
| V/T | 0.2621 | likely_benign | 0.2384 | benign | -2.52 | Highly Destabilizing | 0.86 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/W | 0.8294 | likely_pathogenic | 0.8058 | pathogenic | -1.864 | Destabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| V/Y | 0.5842 | likely_pathogenic | 0.5488 | ambiguous | -1.562 | Destabilizing | 0.978 | D | 0.727 | 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.