Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22952 | 69079;69080;69081 | chr2:178577481;178577480;178577479 | chr2:179442208;179442207;179442206 |
| N2AB | 21311 | 64156;64157;64158 | chr2:178577481;178577480;178577479 | chr2:179442208;179442207;179442206 |
| N2A | 20384 | 61375;61376;61377 | chr2:178577481;178577480;178577479 | chr2:179442208;179442207;179442206 |
| N2B | 13887 | 41884;41885;41886 | chr2:178577481;178577480;178577479 | chr2:179442208;179442207;179442206 |
| Novex-1 | 14012 | 42259;42260;42261 | chr2:178577481;178577480;178577479 | chr2:179442208;179442207;179442206 |
| Novex-2 | 14079 | 42460;42461;42462 | chr2:178577481;178577480;178577479 | chr2:179442208;179442207;179442206 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs2046685725  |
None | 0.007 | N | 0.233 | 0.058 | 0.32580497728 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs2046685725 |
None | 0.007 | N | 0.233 | 0.058 | 0.32580497728 | gnomAD-4.0.0 | 3.76378E-06 | None | None | None | None | N | None | 0 | 3.3653E-05 | None | 0 | 0 | None | 0 | 0 | 3.42608E-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 | 0.4259 | ambiguous | 0.3593 | ambiguous | -1.499 | Destabilizing | 0.4 | N | 0.495 | neutral | None | None | None | None | N |
| I/C | 0.7395 | likely_pathogenic | 0.6539 | pathogenic | -1.025 | Destabilizing | 0.992 | D | 0.517 | neutral | None | None | None | None | N |
| I/D | 0.8252 | likely_pathogenic | 0.778 | pathogenic | -0.747 | Destabilizing | 0.972 | D | 0.601 | neutral | None | None | None | None | N |
| I/E | 0.7157 | likely_pathogenic | 0.677 | pathogenic | -0.74 | Destabilizing | 0.92 | D | 0.586 | neutral | None | None | None | None | N |
| I/F | 0.2219 | likely_benign | 0.1796 | benign | -1.01 | Destabilizing | 0.447 | N | 0.515 | neutral | None | None | None | None | N |
| I/G | 0.737 | likely_pathogenic | 0.668 | pathogenic | -1.821 | Destabilizing | 0.92 | D | 0.589 | neutral | None | None | None | None | N |
| I/H | 0.698 | likely_pathogenic | 0.6198 | pathogenic | -1.098 | Destabilizing | 0.992 | D | 0.607 | neutral | None | None | None | None | N |
| I/K | 0.6034 | likely_pathogenic | 0.5464 | ambiguous | -1.063 | Destabilizing | 0.896 | D | 0.585 | neutral | N | 0.505387366 | None | None | N |
| I/L | 0.0998 | likely_benign | 0.0924 | benign | -0.695 | Destabilizing | 0.001 | N | 0.193 | neutral | N | 0.383708949 | None | None | N |
| I/M | 0.0971 | likely_benign | 0.0908 | benign | -0.638 | Destabilizing | 0.045 | N | 0.241 | neutral | N | 0.460980441 | None | None | N |
| I/N | 0.4012 | ambiguous | 0.3678 | ambiguous | -0.882 | Destabilizing | 0.972 | D | 0.613 | neutral | None | None | None | None | N |
| I/P | 0.9139 | likely_pathogenic | 0.8732 | pathogenic | -0.93 | Destabilizing | 0.972 | D | 0.605 | neutral | None | None | None | None | N |
| I/Q | 0.5837 | likely_pathogenic | 0.5222 | ambiguous | -1.012 | Destabilizing | 0.92 | D | 0.613 | neutral | None | None | None | None | N |
| I/R | 0.5181 | ambiguous | 0.4484 | ambiguous | -0.558 | Destabilizing | 0.896 | D | 0.601 | neutral | D | 0.524146485 | None | None | N |
| I/S | 0.4155 | ambiguous | 0.3783 | ambiguous | -1.503 | Destabilizing | 0.766 | D | 0.547 | neutral | None | None | None | None | N |
| I/T | 0.3783 | ambiguous | 0.3194 | benign | -1.372 | Destabilizing | 0.549 | D | 0.5 | neutral | N | 0.485838813 | None | None | N |
| I/V | 0.0728 | likely_benign | 0.0633 | benign | -0.93 | Destabilizing | 0.007 | N | 0.233 | neutral | N | 0.427270512 | None | None | N |
| I/W | 0.8449 | likely_pathogenic | 0.791 | pathogenic | -1.079 | Destabilizing | 0.992 | D | 0.629 | neutral | None | None | None | None | N |
| I/Y | 0.5666 | likely_pathogenic | 0.5076 | ambiguous | -0.852 | Destabilizing | 0.92 | D | 0.528 | 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.