Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23117 | 69574;69575;69576 | chr2:178576986;178576985;178576984 | chr2:179441713;179441712;179441711 |
| N2AB | 21476 | 64651;64652;64653 | chr2:178576986;178576985;178576984 | chr2:179441713;179441712;179441711 |
| N2A | 20549 | 61870;61871;61872 | chr2:178576986;178576985;178576984 | chr2:179441713;179441712;179441711 |
| N2B | 14052 | 42379;42380;42381 | chr2:178576986;178576985;178576984 | chr2:179441713;179441712;179441711 |
| Novex-1 | 14177 | 42754;42755;42756 | chr2:178576986;178576985;178576984 | chr2:179441713;179441712;179441711 |
| Novex-2 | 14244 | 42955;42956;42957 | chr2:178576986;178576985;178576984 | chr2:179441713;179441712;179441711 |
| 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 | 0.892 | N | 0.445 | 0.328 | 0.65945967189 | gnomAD-4.0.0 | 1.59183E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85966E-06 | 0 | 0 |
| V/G | rs968207606  |
None | 0.967 | D | 0.721 | 0.529 | 0.839645419952 | 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 |
| V/G | rs968207606 |
None | 0.967 | D | 0.721 | 0.529 | 0.839645419952 | gnomAD-4.0.0 | 2.56316E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78831E-06 | 0 | 0 |
| V/I | None | None | 0.873 | N | 0.483 | 0.307 | 0.643257150579 | gnomAD-4.0.0 | 1.59185E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85966E-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 | 0.3205 | likely_benign | 0.2609 | benign | -1.953 | Destabilizing | 0.892 | D | 0.445 | neutral | N | 0.48895065 | None | None | I |
| V/C | 0.7562 | likely_pathogenic | 0.6588 | pathogenic | -1.839 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | I |
| V/D | 0.8224 | likely_pathogenic | 0.7819 | pathogenic | -2.369 | Highly Destabilizing | 0.95 | D | 0.715 | prob.delet. | None | None | None | None | I |
| V/E | 0.423 | ambiguous | 0.3842 | ambiguous | -2.237 | Highly Destabilizing | 0.056 | N | 0.407 | neutral | N | 0.482913151 | None | None | I |
| V/F | 0.3052 | likely_benign | 0.2492 | benign | -1.284 | Destabilizing | 0.996 | D | 0.783 | deleterious | None | None | None | None | I |
| V/G | 0.5794 | likely_pathogenic | 0.4902 | ambiguous | -2.37 | Highly Destabilizing | 0.967 | D | 0.721 | prob.delet. | D | 0.525781498 | None | None | I |
| V/H | 0.7625 | likely_pathogenic | 0.7081 | pathogenic | -1.879 | Destabilizing | 0.997 | D | 0.789 | deleterious | None | None | None | None | I |
| V/I | 0.0771 | likely_benign | 0.073 | benign | -0.831 | Destabilizing | 0.873 | D | 0.483 | neutral | N | 0.485316573 | None | None | I |
| V/K | 0.4926 | ambiguous | 0.4513 | ambiguous | -1.455 | Destabilizing | 0.95 | D | 0.671 | neutral | None | None | None | None | I |
| V/L | 0.2989 | likely_benign | 0.228 | benign | -0.831 | Destabilizing | 0.773 | D | 0.462 | neutral | N | 0.505026989 | None | None | I |
| V/M | 0.1566 | likely_benign | 0.1239 | benign | -1.072 | Destabilizing | 0.996 | D | 0.629 | neutral | None | None | None | None | I |
| V/N | 0.6163 | likely_pathogenic | 0.5234 | ambiguous | -1.616 | Destabilizing | 0.975 | D | 0.809 | deleterious | None | None | None | None | I |
| V/P | 0.9899 | likely_pathogenic | 0.9864 | pathogenic | -1.178 | Destabilizing | 0.987 | D | 0.763 | deleterious | None | None | None | None | I |
| V/Q | 0.3903 | ambiguous | 0.3323 | benign | -1.636 | Destabilizing | 0.95 | D | 0.755 | deleterious | None | None | None | None | I |
| V/R | 0.4724 | ambiguous | 0.4338 | ambiguous | -1.159 | Destabilizing | 0.975 | D | 0.811 | deleterious | None | None | None | None | I |
| V/S | 0.4211 | ambiguous | 0.3387 | benign | -2.223 | Highly Destabilizing | 0.975 | D | 0.668 | neutral | None | None | None | None | I |
| V/T | 0.27 | likely_benign | 0.2144 | benign | -1.969 | Destabilizing | 0.916 | D | 0.515 | neutral | None | None | None | None | I |
| V/W | 0.9208 | likely_pathogenic | 0.8953 | pathogenic | -1.59 | Destabilizing | 0.999 | D | 0.754 | deleterious | None | None | None | None | I |
| V/Y | 0.7287 | likely_pathogenic | 0.6655 | pathogenic | -1.267 | Destabilizing | 0.996 | D | 0.786 | deleterious | 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.