Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16104 | 48535;48536;48537 | chr2:178616481;178616480;178616479 | chr2:179481208;179481207;179481206 |
| N2AB | 14463 | 43612;43613;43614 | chr2:178616481;178616480;178616479 | chr2:179481208;179481207;179481206 |
| N2A | 13536 | 40831;40832;40833 | chr2:178616481;178616480;178616479 | chr2:179481208;179481207;179481206 |
| N2B | 7039 | 21340;21341;21342 | chr2:178616481;178616480;178616479 | chr2:179481208;179481207;179481206 |
| Novex-1 | 7164 | 21715;21716;21717 | chr2:178616481;178616480;178616479 | chr2:179481208;179481207;179481206 |
| Novex-2 | 7231 | 21916;21917;21918 | chr2:178616481;178616480;178616479 | chr2:179481208;179481207;179481206 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs1399165116  |
None | 0.977 | N | 0.565 | 0.293 | 0.258779203287 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| K/E | rs1399165116 |
None | 0.977 | N | 0.565 | 0.293 | 0.258779203287 | gnomAD-4.0.0 | 3.10166E-06 | None | None | None | None | N | None | 1.33697E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.3934E-06 | 0 | 0 |
| K/T | rs1060500396 |
None | 0.997 | N | 0.709 | 0.343 | 0.344251166708 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.3659 | ambiguous | 0.4048 | ambiguous | -0.332 | Destabilizing | 0.983 | D | 0.609 | neutral | None | None | None | None | N |
| K/C | 0.7434 | likely_pathogenic | 0.7933 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| K/D | 0.6966 | likely_pathogenic | 0.7327 | pathogenic | -0.157 | Destabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| K/E | 0.2496 | likely_benign | 0.2729 | benign | -0.086 | Destabilizing | 0.977 | D | 0.565 | neutral | N | 0.470121005 | None | None | N |
| K/F | 0.872 | likely_pathogenic | 0.9038 | pathogenic | -0.119 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| K/G | 0.5339 | ambiguous | 0.5924 | pathogenic | -0.662 | Destabilizing | 0.998 | D | 0.614 | neutral | None | None | None | None | N |
| K/H | 0.4035 | ambiguous | 0.4561 | ambiguous | -1.046 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | N |
| K/I | 0.4855 | ambiguous | 0.5172 | ambiguous | 0.503 | Stabilizing | 0.997 | D | 0.742 | deleterious | N | 0.482259942 | None | None | N |
| K/L | 0.45 | ambiguous | 0.4917 | ambiguous | 0.503 | Stabilizing | 0.995 | D | 0.614 | neutral | None | None | None | None | N |
| K/M | 0.3261 | likely_benign | 0.3508 | ambiguous | 0.369 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| K/N | 0.5273 | ambiguous | 0.558 | ambiguous | -0.305 | Destabilizing | 0.993 | D | 0.707 | prob.neutral | N | 0.480757068 | None | None | N |
| K/P | 0.4984 | ambiguous | 0.5094 | ambiguous | 0.255 | Stabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| K/Q | 0.1789 | likely_benign | 0.201 | benign | -0.426 | Destabilizing | 0.993 | D | 0.693 | prob.neutral | N | 0.47757935 | None | None | N |
| K/R | 0.0804 | likely_benign | 0.0874 | benign | -0.591 | Destabilizing | 0.235 | N | 0.27 | neutral | N | 0.479874733 | None | None | N |
| K/S | 0.5052 | ambiguous | 0.5428 | ambiguous | -0.87 | Destabilizing | 0.983 | D | 0.643 | neutral | None | None | None | None | N |
| K/T | 0.2153 | likely_benign | 0.2327 | benign | -0.616 | Destabilizing | 0.997 | D | 0.709 | prob.delet. | N | 0.462446546 | None | None | N |
| K/V | 0.3816 | ambiguous | 0.4105 | ambiguous | 0.255 | Stabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | N |
| K/W | 0.8354 | likely_pathogenic | 0.8787 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7537 | likely_pathogenic | 0.8012 | pathogenic | 0.251 | Stabilizing | 0.999 | D | 0.727 | 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.