Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25819 | 77680;77681;77682 | chr2:178568677;178568676;178568675 | chr2:179433404;179433403;179433402 |
| N2AB | 24178 | 72757;72758;72759 | chr2:178568677;178568676;178568675 | chr2:179433404;179433403;179433402 |
| N2A | 23251 | 69976;69977;69978 | chr2:178568677;178568676;178568675 | chr2:179433404;179433403;179433402 |
| N2B | 16754 | 50485;50486;50487 | chr2:178568677;178568676;178568675 | chr2:179433404;179433403;179433402 |
| Novex-1 | 16879 | 50860;50861;50862 | chr2:178568677;178568676;178568675 | chr2:179433404;179433403;179433402 |
| Novex-2 | 16946 | 51061;51062;51063 | chr2:178568677;178568676;178568675 | chr2:179433404;179433403;179433402 |
| 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/L | rs764950661  |
None | 0.014 | N | 0.411 | 0.116 | 0.300110245524 | 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/L | rs764950661 |
None | 0.014 | N | 0.411 | 0.116 | 0.300110245524 | gnomAD-4.0.0 | 6.57834E-06 | None | None | None | None | N | None | 0 | 6.56082E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs764950661 |
None | 0.942 | N | 0.69 | 0.254 | 0.417334834585 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| V/M | rs764950661 |
None | 0.942 | N | 0.69 | 0.254 | 0.417334834585 | gnomAD-4.0.0 | 5.57896E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23274E-05 | None | 0 | 0 | 5.9344E-06 | 0 | 1.60149E-05 |
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 | 0.5483 | ambiguous | 0.5251 | ambiguous | -1.951 | Destabilizing | 0.058 | N | 0.443 | neutral | N | 0.468041621 | None | None | N |
| V/C | 0.8176 | likely_pathogenic | 0.8107 | pathogenic | -1.484 | Destabilizing | 0.998 | D | 0.799 | deleterious | None | None | None | None | N |
| V/D | 0.985 | likely_pathogenic | 0.9841 | pathogenic | -2.996 | Highly Destabilizing | 0.978 | D | 0.867 | deleterious | None | None | None | None | N |
| V/E | 0.9726 | likely_pathogenic | 0.9711 | pathogenic | -2.746 | Highly Destabilizing | 0.97 | D | 0.83 | deleterious | N | 0.498247408 | None | None | N |
| V/F | 0.3174 | likely_benign | 0.3337 | benign | -1.159 | Destabilizing | 0.956 | D | 0.81 | deleterious | None | None | None | None | N |
| V/G | 0.7654 | likely_pathogenic | 0.7575 | pathogenic | -2.509 | Highly Destabilizing | 0.89 | D | 0.849 | deleterious | N | 0.475281307 | None | None | N |
| V/H | 0.9798 | likely_pathogenic | 0.9805 | pathogenic | -2.451 | Highly Destabilizing | 0.998 | D | 0.869 | deleterious | None | None | None | None | N |
| V/I | 0.0696 | likely_benign | 0.0709 | benign | -0.38 | Destabilizing | 0.019 | N | 0.337 | neutral | None | None | None | None | N |
| V/K | 0.9815 | likely_pathogenic | 0.9818 | pathogenic | -1.796 | Destabilizing | 0.956 | D | 0.827 | deleterious | None | None | None | None | N |
| V/L | 0.2362 | likely_benign | 0.2448 | benign | -0.38 | Destabilizing | 0.014 | N | 0.411 | neutral | N | 0.455909605 | None | None | N |
| V/M | 0.2379 | likely_benign | 0.2386 | benign | -0.426 | Destabilizing | 0.942 | D | 0.69 | prob.neutral | N | 0.497993918 | None | None | N |
| V/N | 0.9406 | likely_pathogenic | 0.9409 | pathogenic | -2.235 | Highly Destabilizing | 0.993 | D | 0.853 | deleterious | None | None | None | None | N |
| V/P | 0.9781 | likely_pathogenic | 0.9803 | pathogenic | -0.878 | Destabilizing | 0.978 | D | 0.839 | deleterious | None | None | None | None | N |
| V/Q | 0.9626 | likely_pathogenic | 0.9635 | pathogenic | -2.026 | Highly Destabilizing | 0.993 | D | 0.832 | deleterious | None | None | None | None | N |
| V/R | 0.971 | likely_pathogenic | 0.9726 | pathogenic | -1.699 | Destabilizing | 0.978 | D | 0.859 | deleterious | None | None | None | None | N |
| V/S | 0.8176 | likely_pathogenic | 0.8057 | pathogenic | -2.766 | Highly Destabilizing | 0.915 | D | 0.827 | deleterious | None | None | None | None | N |
| V/T | 0.709 | likely_pathogenic | 0.7045 | pathogenic | -2.372 | Highly Destabilizing | 0.86 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/W | 0.961 | likely_pathogenic | 0.9622 | pathogenic | -1.817 | Destabilizing | 0.998 | D | 0.863 | deleterious | None | None | None | None | N |
| V/Y | 0.8626 | likely_pathogenic | 0.8676 | pathogenic | -1.36 | Destabilizing | 0.978 | D | 0.791 | 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.