Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16767 | 50524;50525;50526 | chr2:178612112;178612111;178612110 | chr2:179476839;179476838;179476837 |
| N2AB | 15126 | 45601;45602;45603 | chr2:178612112;178612111;178612110 | chr2:179476839;179476838;179476837 |
| N2A | 14199 | 42820;42821;42822 | chr2:178612112;178612111;178612110 | chr2:179476839;179476838;179476837 |
| N2B | 7702 | 23329;23330;23331 | chr2:178612112;178612111;178612110 | chr2:179476839;179476838;179476837 |
| Novex-1 | 7827 | 23704;23705;23706 | chr2:178612112;178612111;178612110 | chr2:179476839;179476838;179476837 |
| Novex-2 | 7894 | 23905;23906;23907 | chr2:178612112;178612111;178612110 | chr2:179476839;179476838;179476837 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/P | rs373892279  |
-0.663 | 0.999 | D | 0.766 | 0.466 | None | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| H/P | rs373892279 |
-0.663 | 0.999 | D | 0.766 | 0.466 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| H/P | rs373892279 |
-0.663 | 0.999 | D | 0.766 | 0.466 | None | gnomAD-4.0.0 | 6.57981E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47197E-05 | 0 | 0 |
| H/Y | rs2056436094 |
None | 0.219 | N | 0.123 | 0.275 | 0.231231049324 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.6906 | likely_pathogenic | 0.6776 | pathogenic | -1.059 | Destabilizing | 0.993 | D | 0.671 | neutral | None | None | None | None | N |
| H/C | 0.3537 | ambiguous | 0.3425 | ambiguous | -0.34 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| H/D | 0.7382 | likely_pathogenic | 0.7096 | pathogenic | -0.802 | Destabilizing | 0.999 | D | 0.672 | neutral | N | 0.478363644 | None | None | N |
| H/E | 0.7675 | likely_pathogenic | 0.7519 | pathogenic | -0.706 | Destabilizing | 0.998 | D | 0.552 | neutral | None | None | None | None | N |
| H/F | 0.3849 | ambiguous | 0.4088 | ambiguous | 0.002 | Stabilizing | 0.971 | D | 0.643 | neutral | None | None | None | None | N |
| H/G | 0.7298 | likely_pathogenic | 0.7412 | pathogenic | -1.405 | Destabilizing | 0.998 | D | 0.694 | prob.neutral | None | None | None | None | N |
| H/I | 0.7344 | likely_pathogenic | 0.7209 | pathogenic | -0.101 | Destabilizing | 0.998 | D | 0.782 | deleterious | None | None | None | None | N |
| H/K | 0.7939 | likely_pathogenic | 0.7963 | pathogenic | -0.954 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| H/L | 0.4491 | ambiguous | 0.4304 | ambiguous | -0.101 | Destabilizing | 0.98 | D | 0.723 | prob.delet. | N | 0.506408803 | None | None | N |
| H/M | 0.751 | likely_pathogenic | 0.7441 | pathogenic | -0.2 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| H/N | 0.3042 | likely_benign | 0.2825 | benign | -0.954 | Destabilizing | 0.997 | D | 0.556 | neutral | N | 0.478363644 | None | None | N |
| H/P | 0.9672 | likely_pathogenic | 0.9647 | pathogenic | -0.402 | Destabilizing | 0.999 | D | 0.766 | deleterious | D | 0.549401257 | None | None | N |
| H/Q | 0.5585 | ambiguous | 0.5371 | ambiguous | -0.707 | Destabilizing | 0.999 | D | 0.547 | neutral | N | 0.475974776 | None | None | N |
| H/R | 0.5339 | ambiguous | 0.5293 | ambiguous | -1.286 | Destabilizing | 0.997 | D | 0.543 | neutral | N | 0.474811033 | None | None | N |
| H/S | 0.5327 | ambiguous | 0.4989 | ambiguous | -1.041 | Destabilizing | 0.993 | D | 0.645 | neutral | None | None | None | None | N |
| H/T | 0.6453 | likely_pathogenic | 0.6077 | pathogenic | -0.852 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| H/V | 0.6443 | likely_pathogenic | 0.6378 | pathogenic | -0.402 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | N |
| H/W | 0.5709 | likely_pathogenic | 0.6053 | pathogenic | 0.223 | Stabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| H/Y | 0.1579 | likely_benign | 0.1675 | benign | 0.386 | Stabilizing | 0.219 | N | 0.123 | neutral | N | 0.465497721 | 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.