Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2606 | 8041;8042;8043 | chr2:178773148;178773147;178773146 | chr2:179637875;179637874;179637873 |
| N2AB | 2606 | 8041;8042;8043 | chr2:178773148;178773147;178773146 | chr2:179637875;179637874;179637873 |
| N2A | 2606 | 8041;8042;8043 | chr2:178773148;178773147;178773146 | chr2:179637875;179637874;179637873 |
| N2B | 2560 | 7903;7904;7905 | chr2:178773148;178773147;178773146 | chr2:179637875;179637874;179637873 |
| Novex-1 | 2560 | 7903;7904;7905 | chr2:178773148;178773147;178773146 | chr2:179637875;179637874;179637873 |
| Novex-2 | 2560 | 7903;7904;7905 | chr2:178773148;178773147;178773146 | chr2:179637875;179637874;179637873 |
| Novex-3 | 2606 | 8041;8042;8043 | chr2:178773148;178773147;178773146 | chr2:179637875;179637874;179637873 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.999 | D | 0.612 | 0.799 | 0.626812710122 | gnomAD-4.0.0 | 6.8419E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15972E-05 | 0 |
| A/T | rs375286376  |
-1.061 | 1.0 | D | 0.745 | 0.645 | None | gnomAD-2.1.1 | 3.55E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 3.99E-05 | 5.44E-05 | 0 |
| A/T | rs375286376 |
-1.061 | 1.0 | D | 0.745 | 0.645 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 2.07039E-04 | 4.78469E-04 |
| A/T | rs375286376 |
-1.061 | 1.0 | D | 0.745 | 0.645 | None | gnomAD-4.0.0 | 6.87847E-05 | None | None | None | None | N | None | 2.6703E-05 | 1.66789E-05 | None | 0 | 0 | None | 4.68794E-05 | 0 | 8.39034E-05 | 4.39261E-05 | 3.20164E-05 |
| A/V | rs370857722 |
0.501 | 0.999 | D | 0.601 | 0.603 | None | gnomAD-2.1.1 | 6.74E-05 | None | None | None | None | N | None | 4.02E-05 | 0 | None | 5.79262E-04 | 0 | None | 6.54E-05 | None | 0 | 7E-05 | 1.39315E-04 |
| A/V | rs370857722 |
0.501 | 0.999 | D | 0.601 | 0.603 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92678E-04 | None | 0 | 3.16456E-03 | 1.02935E-04 | 2.07814E-04 | 4.78469E-04 |
| A/V | rs370857722 |
0.501 | 0.999 | D | 0.601 | 0.603 | None | gnomAD-4.0.0 | 6.75444E-05 | None | None | None | None | N | None | 1.33355E-05 | 0 | None | 2.70289E-04 | 2.23125E-05 | None | 0 | 6.60066E-04 | 6.94981E-05 | 6.5908E-05 | 1.12018E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6901 | likely_pathogenic | 0.6794 | pathogenic | -0.672 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| A/D | 0.9747 | likely_pathogenic | 0.9744 | pathogenic | -1.417 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| A/E | 0.9727 | likely_pathogenic | 0.9735 | pathogenic | -1.228 | Destabilizing | 1.0 | D | 0.85 | deleterious | D | 0.695731637 | None | None | N |
| A/F | 0.9061 | likely_pathogenic | 0.898 | pathogenic | -0.359 | Destabilizing | 0.999 | D | 0.857 | deleterious | None | None | None | None | N |
| A/G | 0.3633 | ambiguous | 0.3565 | ambiguous | -1.116 | Destabilizing | 0.999 | D | 0.612 | neutral | D | 0.733138735 | None | None | N |
| A/H | 0.9703 | likely_pathogenic | 0.9696 | pathogenic | -1.627 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| A/I | 0.729 | likely_pathogenic | 0.7083 | pathogenic | 0.635 | Stabilizing | 0.998 | D | 0.835 | deleterious | None | None | None | None | N |
| A/K | 0.9858 | likely_pathogenic | 0.9859 | pathogenic | -0.864 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| A/L | 0.6824 | likely_pathogenic | 0.6676 | pathogenic | 0.635 | Stabilizing | 0.994 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/M | 0.7932 | likely_pathogenic | 0.781 | pathogenic | 0.353 | Stabilizing | 0.985 | D | 0.673 | neutral | None | None | None | None | N |
| A/N | 0.9504 | likely_pathogenic | 0.9505 | pathogenic | -1.062 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| A/P | 0.9741 | likely_pathogenic | 0.9772 | pathogenic | 0.26 | Stabilizing | 1.0 | D | 0.871 | deleterious | D | 0.657455962 | None | None | N |
| A/Q | 0.9553 | likely_pathogenic | 0.9563 | pathogenic | -0.842 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| A/R | 0.9618 | likely_pathogenic | 0.962 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| A/S | 0.2609 | likely_benign | 0.26 | benign | -1.519 | Destabilizing | 0.999 | D | 0.607 | neutral | D | 0.673946774 | None | None | N |
| A/T | 0.3749 | ambiguous | 0.3615 | ambiguous | -1.184 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.618841109 | None | None | N |
| A/V | 0.4054 | ambiguous | 0.3819 | ambiguous | 0.26 | Stabilizing | 0.999 | D | 0.601 | neutral | D | 0.530340081 | None | None | N |
| A/W | 0.9889 | likely_pathogenic | 0.9884 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| A/Y | 0.9574 | likely_pathogenic | 0.9567 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.883 | 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.