Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19950 | 60073;60074;60075 | chr2:178592056;178592055;178592054 | chr2:179456783;179456782;179456781 |
| N2AB | 18309 | 55150;55151;55152 | chr2:178592056;178592055;178592054 | chr2:179456783;179456782;179456781 |
| N2A | 17382 | 52369;52370;52371 | chr2:178592056;178592055;178592054 | chr2:179456783;179456782;179456781 |
| N2B | 10885 | 32878;32879;32880 | chr2:178592056;178592055;178592054 | chr2:179456783;179456782;179456781 |
| Novex-1 | 11010 | 33253;33254;33255 | chr2:178592056;178592055;178592054 | chr2:179456783;179456782;179456781 |
| Novex-2 | 11077 | 33454;33455;33456 | chr2:178592056;178592055;178592054 | chr2:179456783;179456782;179456781 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs374914334  |
None | 0.991 | N | 0.601 | 0.489 | 0.734535655235 | gnomAD-4.0.0 | 6.84528E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1599E-05 | 0 |
| R/Q | rs374914334 |
-1.105 | 1.0 | N | 0.55 | 0.362 | None | gnomAD-2.1.1 | 9.67E-05 | None | None | None | None | N | None | 2.06731E-04 | 2.84E-05 | None | 0 | 3.11785E-04 | None | 6.54E-05 | None | 4.01E-05 | 9.4E-05 | 0 |
| R/Q | rs374914334 |
-1.105 | 1.0 | N | 0.55 | 0.362 | None | gnomAD-3.1.2 | 1.11789E-04 | None | None | None | None | N | None | 1.93106E-04 | 6.55E-05 | 0 | 0 | 7.74893E-04 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/Q | rs374914334 |
-1.105 | 1.0 | N | 0.55 | 0.362 | None | gnomAD-4.0.0 | 1.14078E-04 | None | None | None | None | N | None | 1.73602E-04 | 5.00835E-05 | None | 0 | 1.65785E-03 | None | 1.56362E-05 | 0 | 7.63021E-05 | 3.29504E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9798 | likely_pathogenic | 0.9645 | pathogenic | -2.049 | Highly Destabilizing | 0.992 | D | 0.572 | neutral | None | None | None | None | N |
| R/C | 0.717 | likely_pathogenic | 0.6487 | pathogenic | -1.815 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/D | 0.9988 | likely_pathogenic | 0.9981 | pathogenic | -1.281 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/E | 0.9776 | likely_pathogenic | 0.9654 | pathogenic | -1.07 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| R/F | 0.9942 | likely_pathogenic | 0.9919 | pathogenic | -1.072 | Destabilizing | 0.998 | D | 0.764 | deleterious | None | None | None | None | N |
| R/G | 0.9762 | likely_pathogenic | 0.9608 | pathogenic | -2.344 | Highly Destabilizing | 0.998 | D | 0.595 | neutral | D | 0.545096613 | None | None | N |
| R/H | 0.6383 | likely_pathogenic | 0.5838 | pathogenic | -2.113 | Highly Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | N |
| R/I | 0.9769 | likely_pathogenic | 0.9664 | pathogenic | -1.174 | Destabilizing | 0.995 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/K | 0.4612 | ambiguous | 0.4202 | ambiguous | -1.259 | Destabilizing | 0.99 | D | 0.637 | neutral | None | None | None | None | N |
| R/L | 0.9448 | likely_pathogenic | 0.9222 | pathogenic | -1.174 | Destabilizing | 0.991 | D | 0.601 | neutral | N | 0.515889542 | None | None | N |
| R/M | 0.9712 | likely_pathogenic | 0.9532 | pathogenic | -1.705 | Destabilizing | 0.96 | D | 0.565 | neutral | None | None | None | None | N |
| R/N | 0.9952 | likely_pathogenic | 0.9925 | pathogenic | -1.44 | Destabilizing | 1.0 | D | 0.527 | neutral | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -1.46 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | D | 0.545603592 | None | None | N |
| R/Q | 0.5378 | ambiguous | 0.416 | ambiguous | -1.181 | Destabilizing | 1.0 | D | 0.55 | neutral | N | 0.492212199 | None | None | N |
| R/S | 0.9894 | likely_pathogenic | 0.9811 | pathogenic | -2.144 | Highly Destabilizing | 0.996 | D | 0.546 | neutral | None | None | None | None | N |
| R/T | 0.9852 | likely_pathogenic | 0.9732 | pathogenic | -1.751 | Destabilizing | 0.996 | D | 0.549 | neutral | None | None | None | None | N |
| R/V | 0.9755 | likely_pathogenic | 0.9633 | pathogenic | -1.46 | Destabilizing | 0.983 | D | 0.659 | neutral | None | None | None | None | N |
| R/W | 0.9327 | likely_pathogenic | 0.9122 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/Y | 0.9821 | likely_pathogenic | 0.9756 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.717 | 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.