Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3319 | 10180;10181;10182 | chr2:178764560;178764559;178764558 | chr2:179629287;179629286;179629285 |
| N2AB | 3319 | 10180;10181;10182 | chr2:178764560;178764559;178764558 | chr2:179629287;179629286;179629285 |
| N2A | 3319 | 10180;10181;10182 | chr2:178764560;178764559;178764558 | chr2:179629287;179629286;179629285 |
| N2B | 3273 | 10042;10043;10044 | chr2:178764560;178764559;178764558 | chr2:179629287;179629286;179629285 |
| Novex-1 | 3273 | 10042;10043;10044 | chr2:178764560;178764559;178764558 | chr2:179629287;179629286;179629285 |
| Novex-2 | 3273 | 10042;10043;10044 | chr2:178764560;178764559;178764558 | chr2:179629287;179629286;179629285 |
| Novex-3 | 3319 | 10180;10181;10182 | chr2:178764560;178764559;178764558 | chr2:179629287;179629286;179629285 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs375533809  |
-0.331 | 0.001 | N | 0.162 | 0.048 | None | gnomAD-2.1.1 | 5.32E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.1673E-04 | 0 |
| V/I | rs375533809 |
-0.331 | 0.001 | N | 0.162 | 0.048 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.91103E-04 | 0 | 0 |
| V/I | rs375533809 |
-0.331 | 0.001 | N | 0.162 | 0.048 | None | gnomAD-4.0.0 | 5.01858E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.77959E-05 | 0 | 1.60051E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3604 | ambiguous | 0.1591 | benign | -0.845 | Destabilizing | 0.003 | N | 0.129 | neutral | N | 0.481485191 | None | None | I |
| V/C | 0.8993 | likely_pathogenic | 0.7484 | pathogenic | -0.637 | Destabilizing | 0.981 | D | 0.491 | neutral | None | None | None | None | I |
| V/D | 0.6397 | likely_pathogenic | 0.3582 | ambiguous | -0.764 | Destabilizing | 0.627 | D | 0.568 | neutral | N | 0.506516677 | None | None | I |
| V/E | 0.4783 | ambiguous | 0.2193 | benign | -0.882 | Destabilizing | 0.388 | N | 0.555 | neutral | None | None | None | None | I |
| V/F | 0.2596 | likely_benign | 0.1484 | benign | -1.023 | Destabilizing | 0.627 | D | 0.496 | neutral | N | 0.510947883 | None | None | I |
| V/G | 0.5362 | ambiguous | 0.272 | benign | -1.001 | Destabilizing | 0.324 | N | 0.574 | neutral | D | 0.564182223 | None | None | I |
| V/H | 0.7928 | likely_pathogenic | 0.5145 | ambiguous | -0.542 | Destabilizing | 0.981 | D | 0.579 | neutral | None | None | None | None | I |
| V/I | 0.078 | likely_benign | 0.0651 | benign | -0.573 | Destabilizing | 0.001 | N | 0.162 | neutral | N | 0.50053257 | None | None | I |
| V/K | 0.5667 | likely_pathogenic | 0.2751 | benign | -0.715 | Destabilizing | 0.388 | N | 0.561 | neutral | None | None | None | None | I |
| V/L | 0.3546 | ambiguous | 0.1723 | benign | -0.573 | Destabilizing | 0.015 | N | 0.196 | neutral | N | 0.505255696 | None | None | I |
| V/M | 0.2149 | likely_benign | 0.1058 | benign | -0.422 | Destabilizing | 0.054 | N | 0.197 | neutral | None | None | None | None | I |
| V/N | 0.4957 | ambiguous | 0.2321 | benign | -0.376 | Destabilizing | 0.69 | D | 0.573 | neutral | None | None | None | None | I |
| V/P | 0.9499 | likely_pathogenic | 0.8171 | pathogenic | -0.629 | Destabilizing | 0.818 | D | 0.559 | neutral | None | None | None | None | I |
| V/Q | 0.5496 | ambiguous | 0.2739 | benign | -0.694 | Destabilizing | 0.818 | D | 0.581 | neutral | None | None | None | None | I |
| V/R | 0.5144 | ambiguous | 0.2515 | benign | -0.085 | Destabilizing | 0.818 | D | 0.584 | neutral | None | None | None | None | I |
| V/S | 0.437 | ambiguous | 0.1843 | benign | -0.723 | Destabilizing | 0.024 | N | 0.41 | neutral | None | None | None | None | I |
| V/T | 0.3151 | likely_benign | 0.1379 | benign | -0.75 | Destabilizing | 0.008 | N | 0.149 | neutral | None | None | None | None | I |
| V/W | 0.9216 | likely_pathogenic | 0.756 | pathogenic | -1.072 | Destabilizing | 0.981 | D | 0.603 | neutral | None | None | None | None | I |
| V/Y | 0.7276 | likely_pathogenic | 0.4974 | ambiguous | -0.8 | Destabilizing | 0.818 | D | 0.499 | neutral | None | None | None | None | I |
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.