Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21471 | 64636;64637;64638 | chr2:178585333;178585332;178585331 | chr2:179450060;179450059;179450058 |
| N2AB | 19830 | 59713;59714;59715 | chr2:178585333;178585332;178585331 | chr2:179450060;179450059;179450058 |
| N2A | 18903 | 56932;56933;56934 | chr2:178585333;178585332;178585331 | chr2:179450060;179450059;179450058 |
| N2B | 12406 | 37441;37442;37443 | chr2:178585333;178585332;178585331 | chr2:179450060;179450059;179450058 |
| Novex-1 | 12531 | 37816;37817;37818 | chr2:178585333;178585332;178585331 | chr2:179450060;179450059;179450058 |
| Novex-2 | 12598 | 38017;38018;38019 | chr2:178585333;178585332;178585331 | chr2:179450060;179450059;179450058 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs774609456  |
-0.988 | 0.994 | N | 0.563 | 0.174 | 0.470970234271 | gnomAD-2.1.1 | 4.44E-05 | None | None | None | None | N | None | 0 | 3.50853E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs774609456 |
-0.988 | 0.994 | N | 0.563 | 0.174 | 0.470970234271 | gnomAD-4.0.0 | 2.17757E-05 | None | None | None | None | N | None | 0 | 3.51922E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3404 | ambiguous | 0.2818 | benign | -1.582 | Destabilizing | 0.97 | D | 0.518 | neutral | None | None | None | None | N |
| L/C | 0.5935 | likely_pathogenic | 0.5571 | ambiguous | -0.698 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| L/D | 0.766 | likely_pathogenic | 0.6992 | pathogenic | -1.29 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| L/E | 0.4191 | ambiguous | 0.344 | ambiguous | -1.276 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| L/F | 0.1739 | likely_benign | 0.1524 | benign | -1.101 | Destabilizing | 0.994 | D | 0.563 | neutral | N | 0.493612069 | None | None | N |
| L/G | 0.7402 | likely_pathogenic | 0.6784 | pathogenic | -1.893 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| L/H | 0.2832 | likely_benign | 0.2385 | benign | -1.061 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.493958785 | None | None | N |
| L/I | 0.0876 | likely_benign | 0.0777 | benign | -0.791 | Destabilizing | 0.122 | N | 0.193 | neutral | N | 0.418306234 | None | None | N |
| L/K | 0.3495 | ambiguous | 0.2977 | benign | -1.1 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | N |
| L/M | 0.122 | likely_benign | 0.1119 | benign | -0.561 | Destabilizing | 0.996 | D | 0.596 | neutral | None | None | None | None | N |
| L/N | 0.4518 | ambiguous | 0.3946 | ambiguous | -0.903 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | N |
| L/P | 0.9349 | likely_pathogenic | 0.8962 | pathogenic | -1.026 | Destabilizing | 0.998 | D | 0.719 | prob.delet. | N | 0.464155953 | None | None | N |
| L/Q | 0.2049 | likely_benign | 0.1718 | benign | -1.075 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| L/R | 0.2885 | likely_benign | 0.2422 | benign | -0.475 | Destabilizing | 0.998 | D | 0.699 | prob.neutral | N | 0.449205144 | None | None | N |
| L/S | 0.399 | ambiguous | 0.3358 | benign | -1.416 | Destabilizing | 0.996 | D | 0.655 | neutral | None | None | None | None | N |
| L/T | 0.2655 | likely_benign | 0.2261 | benign | -1.293 | Destabilizing | 0.97 | D | 0.557 | neutral | None | None | None | None | N |
| L/V | 0.0984 | likely_benign | 0.0877 | benign | -1.026 | Destabilizing | 0.248 | N | 0.24 | neutral | N | 0.49239856 | None | None | N |
| L/W | 0.3865 | ambiguous | 0.3225 | benign | -1.207 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| L/Y | 0.3988 | ambiguous | 0.3506 | ambiguous | -0.988 | Destabilizing | 0.999 | D | 0.637 | neutral | 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.