Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29386 | 88381;88382;88383 | chr2:178556998;178556997;178556996 | chr2:179421725;179421724;179421723 |
| N2AB | 27745 | 83458;83459;83460 | chr2:178556998;178556997;178556996 | chr2:179421725;179421724;179421723 |
| N2A | 26818 | 80677;80678;80679 | chr2:178556998;178556997;178556996 | chr2:179421725;179421724;179421723 |
| N2B | 20321 | 61186;61187;61188 | chr2:178556998;178556997;178556996 | chr2:179421725;179421724;179421723 |
| Novex-1 | 20446 | 61561;61562;61563 | chr2:178556998;178556997;178556996 | chr2:179421725;179421724;179421723 |
| Novex-2 | 20513 | 61762;61763;61764 | chr2:178556998;178556997;178556996 | chr2:179421725;179421724;179421723 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs727505102  |
-0.15 | 0.999 | N | 0.532 | 0.419 | 0.405560941015 | gnomAD-2.1.1 | 8.85E-05 | None | None | None | None | N | None | 6.46E-05 | 6.08731E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs727505102 |
-0.15 | 0.999 | N | 0.532 | 0.419 | 0.405560941015 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 1.30976E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs727505102 |
-0.15 | 0.999 | N | 0.532 | 0.419 | 0.405560941015 | gnomAD-4.0.0 | 1.61121E-05 | None | None | None | None | N | None | 1.3349E-05 | 4.16736E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | None | None | 0.826 | N | 0.55 | 0.215 | 0.178374595973 | gnomAD-4.0.0 | 6.84222E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99441E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.3013 | likely_benign | 0.2363 | benign | -0.67 | Destabilizing | 0.863 | D | 0.519 | neutral | None | None | None | None | N |
| S/C | 0.2354 | likely_benign | 0.1888 | benign | -0.213 | Destabilizing | 0.999 | D | 0.532 | neutral | N | 0.491393775 | None | None | N |
| S/D | 0.8754 | likely_pathogenic | 0.8224 | pathogenic | 0.323 | Stabilizing | 0.884 | D | 0.557 | neutral | None | None | None | None | N |
| S/E | 0.971 | likely_pathogenic | 0.9636 | pathogenic | 0.423 | Stabilizing | 0.939 | D | 0.561 | neutral | None | None | None | None | N |
| S/F | 0.9069 | likely_pathogenic | 0.8608 | pathogenic | -0.72 | Destabilizing | 0.997 | D | 0.587 | neutral | None | None | None | None | N |
| S/G | 0.2257 | likely_benign | 0.1856 | benign | -0.996 | Destabilizing | 0.826 | D | 0.55 | neutral | N | 0.47892591 | None | None | N |
| S/H | 0.8715 | likely_pathogenic | 0.8452 | pathogenic | -1.236 | Destabilizing | 0.991 | D | 0.573 | neutral | None | None | None | None | N |
| S/I | 0.6604 | likely_pathogenic | 0.5903 | pathogenic | 0.118 | Stabilizing | 0.976 | D | 0.588 | neutral | N | 0.50868867 | None | None | N |
| S/K | 0.9933 | likely_pathogenic | 0.9905 | pathogenic | 0.096 | Stabilizing | 0.939 | D | 0.557 | neutral | None | None | None | None | N |
| S/L | 0.5293 | ambiguous | 0.4363 | ambiguous | 0.118 | Stabilizing | 0.939 | D | 0.587 | neutral | None | None | None | None | N |
| S/M | 0.7045 | likely_pathogenic | 0.6413 | pathogenic | 0.09 | Stabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| S/N | 0.233 | likely_benign | 0.2059 | benign | -0.165 | Destabilizing | 0.021 | N | 0.227 | neutral | N | 0.361231948 | None | None | N |
| S/P | 0.929 | likely_pathogenic | 0.9068 | pathogenic | -0.109 | Destabilizing | 0.997 | D | 0.607 | neutral | None | None | None | None | N |
| S/Q | 0.9545 | likely_pathogenic | 0.9448 | pathogenic | -0.076 | Destabilizing | 0.991 | D | 0.615 | neutral | None | None | None | None | N |
| S/R | 0.9863 | likely_pathogenic | 0.9798 | pathogenic | -0.126 | Destabilizing | 0.988 | D | 0.607 | neutral | N | 0.500703905 | None | None | N |
| S/T | 0.1915 | likely_benign | 0.1585 | benign | -0.156 | Destabilizing | 0.134 | N | 0.254 | neutral | N | 0.475458743 | None | None | N |
| S/V | 0.6146 | likely_pathogenic | 0.5346 | ambiguous | -0.109 | Destabilizing | 0.939 | D | 0.595 | neutral | None | None | None | None | N |
| S/W | 0.9374 | likely_pathogenic | 0.9142 | pathogenic | -0.757 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| S/Y | 0.8207 | likely_pathogenic | 0.7716 | pathogenic | -0.383 | Destabilizing | 0.997 | D | 0.581 | 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.