Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22758 | 68497;68498;68499 | chr2:178578668;178578667;178578666 | chr2:179443395;179443394;179443393 |
| N2AB | 21117 | 63574;63575;63576 | chr2:178578668;178578667;178578666 | chr2:179443395;179443394;179443393 |
| N2A | 20190 | 60793;60794;60795 | chr2:178578668;178578667;178578666 | chr2:179443395;179443394;179443393 |
| N2B | 13693 | 41302;41303;41304 | chr2:178578668;178578667;178578666 | chr2:179443395;179443394;179443393 |
| Novex-1 | 13818 | 41677;41678;41679 | chr2:178578668;178578667;178578666 | chr2:179443395;179443394;179443393 |
| Novex-2 | 13885 | 41878;41879;41880 | chr2:178578668;178578667;178578666 | chr2:179443395;179443394;179443393 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs397517675  |
-0.255 | 0.999 | N | 0.679 | 0.288 | 0.264547087235 | gnomAD-2.1.1 | 2.16E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.32E-05 | None | 0 | 3.93E-05 | 0 |
| D/N | rs397517675 |
-0.255 | 0.999 | N | 0.679 | 0.288 | 0.264547087235 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| D/N | rs397517675 |
-0.255 | 0.999 | N | 0.679 | 0.288 | 0.264547087235 | gnomAD-4.0.0 | 1.36486E-05 | None | None | None | None | N | None | 1.33704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44181E-05 | 4.41053E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.336 | likely_benign | 0.357 | ambiguous | -0.405 | Destabilizing | 0.977 | D | 0.663 | neutral | N | 0.520983176 | None | None | N |
| D/C | 0.7269 | likely_pathogenic | 0.7559 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| D/E | 0.2147 | likely_benign | 0.2039 | benign | -0.746 | Destabilizing | 0.117 | N | 0.222 | neutral | N | 0.474672096 | None | None | N |
| D/F | 0.7218 | likely_pathogenic | 0.7369 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| D/G | 0.2929 | likely_benign | 0.3178 | benign | -0.688 | Destabilizing | 0.989 | D | 0.647 | neutral | N | 0.470661223 | None | None | N |
| D/H | 0.4249 | ambiguous | 0.4972 | ambiguous | -0.924 | Destabilizing | 1.0 | D | 0.76 | deleterious | D | 0.525562277 | None | None | N |
| D/I | 0.5995 | likely_pathogenic | 0.6091 | pathogenic | 0.317 | Stabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| D/K | 0.6249 | likely_pathogenic | 0.6654 | pathogenic | -0.284 | Destabilizing | 0.99 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/L | 0.5784 | likely_pathogenic | 0.5975 | pathogenic | 0.317 | Stabilizing | 0.995 | D | 0.746 | deleterious | None | None | None | None | N |
| D/M | 0.7341 | likely_pathogenic | 0.7467 | pathogenic | 0.81 | Stabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/N | 0.1117 | likely_benign | 0.1418 | benign | -0.542 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | N | 0.461817442 | None | None | N |
| D/P | 0.957 | likely_pathogenic | 0.9476 | pathogenic | 0.101 | Stabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | N |
| D/Q | 0.4875 | ambiguous | 0.5163 | ambiguous | -0.467 | Destabilizing | 0.99 | D | 0.747 | deleterious | None | None | None | None | N |
| D/R | 0.6173 | likely_pathogenic | 0.6553 | pathogenic | -0.299 | Destabilizing | 0.995 | D | 0.747 | deleterious | None | None | None | None | N |
| D/S | 0.17 | likely_benign | 0.1933 | benign | -0.746 | Destabilizing | 0.983 | D | 0.601 | neutral | None | None | None | None | N |
| D/T | 0.3066 | likely_benign | 0.3318 | benign | -0.523 | Destabilizing | 0.995 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/V | 0.4312 | ambiguous | 0.4487 | ambiguous | 0.101 | Stabilizing | 0.997 | D | 0.751 | deleterious | D | 0.522278189 | None | None | N |
| D/W | 0.9356 | likely_pathogenic | 0.9407 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/Y | 0.3544 | ambiguous | 0.4062 | ambiguous | -0.337 | Destabilizing | 1.0 | D | 0.791 | deleterious | N | 0.478409904 | 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.