Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19953 | 60082;60083;60084 | chr2:178592047;178592046;178592045 | chr2:179456774;179456773;179456772 |
| N2AB | 18312 | 55159;55160;55161 | chr2:178592047;178592046;178592045 | chr2:179456774;179456773;179456772 |
| N2A | 17385 | 52378;52379;52380 | chr2:178592047;178592046;178592045 | chr2:179456774;179456773;179456772 |
| N2B | 10888 | 32887;32888;32889 | chr2:178592047;178592046;178592045 | chr2:179456774;179456773;179456772 |
| Novex-1 | 11013 | 33262;33263;33264 | chr2:178592047;178592046;178592045 | chr2:179456774;179456773;179456772 |
| Novex-2 | 11080 | 33463;33464;33465 | chr2:178592047;178592046;178592045 | chr2:179456774;179456773;179456772 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs754149259  |
-0.818 | 0.999 | D | 0.651 | 0.63 | 0.681116102103 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.56E-05 | 0 |
| A/V | rs754149259 |
-0.818 | 0.999 | D | 0.651 | 0.63 | 0.681116102103 | 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 |
| A/V | rs754149259 |
-0.818 | 0.999 | D | 0.651 | 0.63 | 0.681116102103 | gnomAD-4.0.0 | 3.34796E-05 | None | None | None | None | N | None | 0 | 3.33901E-05 | None | 0 | 0 | None | 0 | 0 | 4.32384E-05 | 1.09844E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8804 | likely_pathogenic | 0.8655 | pathogenic | -1.806 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| A/D | 0.9985 | likely_pathogenic | 0.9981 | pathogenic | -2.573 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| A/E | 0.997 | likely_pathogenic | 0.9963 | pathogenic | -2.359 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | D | 0.563749025 | None | None | N |
| A/F | 0.994 | likely_pathogenic | 0.993 | pathogenic | -0.674 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| A/G | 0.3757 | ambiguous | 0.3428 | ambiguous | -2.342 | Highly Destabilizing | 0.999 | D | 0.622 | neutral | N | 0.521918201 | None | None | N |
| A/H | 0.9985 | likely_pathogenic | 0.9983 | pathogenic | -1.979 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/I | 0.9841 | likely_pathogenic | 0.9798 | pathogenic | -0.923 | Destabilizing | 0.999 | D | 0.82 | deleterious | None | None | None | None | N |
| A/K | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -1.444 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| A/L | 0.9467 | likely_pathogenic | 0.9344 | pathogenic | -0.923 | Destabilizing | 0.997 | D | 0.769 | deleterious | None | None | None | None | N |
| A/M | 0.9763 | likely_pathogenic | 0.97 | pathogenic | -1.445 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| A/N | 0.9959 | likely_pathogenic | 0.9949 | pathogenic | -1.864 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| A/P | 0.856 | likely_pathogenic | 0.7945 | pathogenic | -1.249 | Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.552646209 | None | None | N |
| A/Q | 0.9937 | likely_pathogenic | 0.9929 | pathogenic | -1.571 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| A/R | 0.9955 | likely_pathogenic | 0.995 | pathogenic | -1.526 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| A/S | 0.459 | ambiguous | 0.4355 | ambiguous | -2.195 | Highly Destabilizing | 0.992 | D | 0.603 | neutral | N | 0.507052722 | None | None | N |
| A/T | 0.8758 | likely_pathogenic | 0.841 | pathogenic | -1.887 | Destabilizing | 0.884 | D | 0.424 | neutral | D | 0.541842427 | None | None | N |
| A/V | 0.9013 | likely_pathogenic | 0.8736 | pathogenic | -1.249 | Destabilizing | 0.999 | D | 0.651 | neutral | D | 0.543616854 | None | None | N |
| A/W | 0.9994 | likely_pathogenic | 0.9992 | pathogenic | -1.139 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| A/Y | 0.998 | likely_pathogenic | 0.9976 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.869 | 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.