Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2856 | 8791;8792;8793 | chr2:178770135;178770134;178770133 | chr2:179634862;179634861;179634860 |
| N2AB | 2856 | 8791;8792;8793 | chr2:178770135;178770134;178770133 | chr2:179634862;179634861;179634860 |
| N2A | 2856 | 8791;8792;8793 | chr2:178770135;178770134;178770133 | chr2:179634862;179634861;179634860 |
| N2B | 2810 | 8653;8654;8655 | chr2:178770135;178770134;178770133 | chr2:179634862;179634861;179634860 |
| Novex-1 | 2810 | 8653;8654;8655 | chr2:178770135;178770134;178770133 | chr2:179634862;179634861;179634860 |
| Novex-2 | 2810 | 8653;8654;8655 | chr2:178770135;178770134;178770133 | chr2:179634862;179634861;179634860 |
| Novex-3 | 2856 | 8791;8792;8793 | chr2:178770135;178770134;178770133 | chr2:179634862;179634861;179634860 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs1387078141  |
-1.867 | 0.002 | N | 0.162 | 0.159 | 0.42748209135 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/V | rs1387078141 |
-1.867 | 0.002 | N | 0.162 | 0.159 | 0.42748209135 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1387078141 |
-1.867 | 0.002 | N | 0.162 | 0.159 | 0.42748209135 | gnomAD-4.0.0 | 5.12232E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.56672E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7431 | likely_pathogenic | 0.7985 | pathogenic | -2.538 | Highly Destabilizing | 0.525 | D | 0.503 | neutral | None | None | None | None | N |
| I/C | 0.8482 | likely_pathogenic | 0.8966 | pathogenic | -2.623 | Highly Destabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | N |
| I/D | 0.9942 | likely_pathogenic | 0.9954 | pathogenic | -3.537 | Highly Destabilizing | 0.991 | D | 0.662 | neutral | None | None | None | None | N |
| I/E | 0.9925 | likely_pathogenic | 0.9935 | pathogenic | -3.415 | Highly Destabilizing | 0.974 | D | 0.646 | neutral | None | None | None | None | N |
| I/F | 0.712 | likely_pathogenic | 0.7479 | pathogenic | -1.728 | Destabilizing | 0.934 | D | 0.588 | neutral | N | 0.519538411 | None | None | N |
| I/G | 0.9701 | likely_pathogenic | 0.9802 | pathogenic | -2.962 | Highly Destabilizing | 0.974 | D | 0.641 | neutral | None | None | None | None | N |
| I/H | 0.9833 | likely_pathogenic | 0.9881 | pathogenic | -2.178 | Highly Destabilizing | 0.998 | D | 0.604 | neutral | None | None | None | None | N |
| I/K | 0.9847 | likely_pathogenic | 0.9846 | pathogenic | -2.158 | Highly Destabilizing | 0.974 | D | 0.641 | neutral | None | None | None | None | N |
| I/L | 0.2346 | likely_benign | 0.2792 | benign | -1.345 | Destabilizing | 0.005 | N | 0.186 | neutral | N | 0.47693621 | None | None | N |
| I/M | 0.3387 | likely_benign | 0.3962 | ambiguous | -1.502 | Destabilizing | 0.934 | D | 0.562 | neutral | D | 0.52228439 | None | None | N |
| I/N | 0.9193 | likely_pathogenic | 0.9359 | pathogenic | -2.481 | Highly Destabilizing | 0.989 | D | 0.659 | neutral | N | 0.513457432 | None | None | N |
| I/P | 0.9651 | likely_pathogenic | 0.9672 | pathogenic | -1.722 | Destabilizing | 0.991 | D | 0.667 | neutral | None | None | None | None | N |
| I/Q | 0.9832 | likely_pathogenic | 0.9869 | pathogenic | -2.557 | Highly Destabilizing | 0.991 | D | 0.647 | neutral | None | None | None | None | N |
| I/R | 0.9716 | likely_pathogenic | 0.9724 | pathogenic | -1.593 | Destabilizing | 0.991 | D | 0.661 | neutral | None | None | None | None | N |
| I/S | 0.8417 | likely_pathogenic | 0.8797 | pathogenic | -3.057 | Highly Destabilizing | 0.966 | D | 0.602 | neutral | N | 0.509975109 | None | None | N |
| I/T | 0.6737 | likely_pathogenic | 0.7372 | pathogenic | -2.808 | Highly Destabilizing | 0.801 | D | 0.539 | neutral | N | 0.464323361 | None | None | N |
| I/V | 0.092 | likely_benign | 0.1014 | benign | -1.722 | Destabilizing | 0.002 | N | 0.162 | neutral | N | 0.341205622 | None | None | N |
| I/W | 0.9944 | likely_pathogenic | 0.9953 | pathogenic | -2.0 | Highly Destabilizing | 0.998 | D | 0.631 | neutral | None | None | None | None | N |
| I/Y | 0.9676 | likely_pathogenic | 0.9731 | pathogenic | -1.78 | Destabilizing | 0.991 | D | 0.64 | 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.