Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2226 | 6901;6902;6903 | chr2:178775035;178775034;178775033 | chr2:179639762;179639761;179639760 |
| N2AB | 2226 | 6901;6902;6903 | chr2:178775035;178775034;178775033 | chr2:179639762;179639761;179639760 |
| N2A | 2226 | 6901;6902;6903 | chr2:178775035;178775034;178775033 | chr2:179639762;179639761;179639760 |
| N2B | 2180 | 6763;6764;6765 | chr2:178775035;178775034;178775033 | chr2:179639762;179639761;179639760 |
| Novex-1 | 2180 | 6763;6764;6765 | chr2:178775035;178775034;178775033 | chr2:179639762;179639761;179639760 |
| Novex-2 | 2180 | 6763;6764;6765 | chr2:178775035;178775034;178775033 | chr2:179639762;179639761;179639760 |
| Novex-3 | 2226 | 6901;6902;6903 | chr2:178775035;178775034;178775033 | chr2:179639762;179639761;179639760 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs370438618  |
0.233 | 0.997 | N | 0.491 | 0.418 | None | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.64E-05 | 0 |
| R/K | rs370438618 |
0.233 | 0.997 | N | 0.491 | 0.418 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs370438618 |
0.233 | 0.997 | N | 0.491 | 0.418 | None | gnomAD-4.0.0 | 7.43544E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32238E-06 | 0 | 1.60041E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8624 | likely_pathogenic | 0.8453 | pathogenic | -0.035 | Destabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | N |
| R/C | 0.5397 | ambiguous | 0.4991 | ambiguous | -0.178 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/D | 0.9367 | likely_pathogenic | 0.9271 | pathogenic | -0.141 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| R/E | 0.7599 | likely_pathogenic | 0.7421 | pathogenic | -0.028 | Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | N |
| R/F | 0.9263 | likely_pathogenic | 0.9129 | pathogenic | -0.096 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/G | 0.5234 | ambiguous | 0.4989 | ambiguous | -0.285 | Destabilizing | 1.0 | D | 0.556 | neutral | N | 0.374760561 | None | None | N |
| R/H | 0.2541 | likely_benign | 0.2404 | benign | -1.016 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| R/I | 0.863 | likely_pathogenic | 0.8488 | pathogenic | 0.606 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.564039147 | None | None | N |
| R/K | 0.269 | likely_benign | 0.247 | benign | -0.05 | Destabilizing | 0.997 | D | 0.491 | neutral | N | 0.472055933 | None | None | N |
| R/L | 0.6944 | likely_pathogenic | 0.6697 | pathogenic | 0.606 | Stabilizing | 1.0 | D | 0.556 | neutral | None | None | None | None | N |
| R/M | 0.7629 | likely_pathogenic | 0.7448 | pathogenic | -0.024 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/N | 0.889 | likely_pathogenic | 0.8761 | pathogenic | 0.051 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/P | 0.9582 | likely_pathogenic | 0.9502 | pathogenic | 0.414 | Stabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| R/Q | 0.2201 | likely_benign | 0.2103 | benign | 0.071 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/S | 0.855 | likely_pathogenic | 0.8397 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.617 | neutral | N | 0.505714285 | None | None | N |
| R/T | 0.8055 | likely_pathogenic | 0.7852 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.615 | neutral | N | 0.507159998 | None | None | N |
| R/V | 0.8984 | likely_pathogenic | 0.886 | pathogenic | 0.414 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/W | 0.515 | ambiguous | 0.4919 | ambiguous | -0.144 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/Y | 0.819 | likely_pathogenic | 0.7969 | pathogenic | 0.251 | Stabilizing | 1.0 | D | 0.691 | prob.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.