Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35762 | 107509;107510;107511 | chr2:178528367;178528366;178528365 | chr2:179393094;179393093;179393092 |
| N2AB | 34121 | 102586;102587;102588 | chr2:178528367;178528366;178528365 | chr2:179393094;179393093;179393092 |
| N2A | 33194 | 99805;99806;99807 | chr2:178528367;178528366;178528365 | chr2:179393094;179393093;179393092 |
| N2B | 26697 | 80314;80315;80316 | chr2:178528367;178528366;178528365 | chr2:179393094;179393093;179393092 |
| Novex-1 | 26822 | 80689;80690;80691 | chr2:178528367;178528366;178528365 | chr2:179393094;179393093;179393092 |
| Novex-2 | 26889 | 80890;80891;80892 | chr2:178528367;178528366;178528365 | chr2:179393094;179393093;179393092 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.068 | N | 0.255 | 0.14 | 0.278143212241 | gnomAD-4.0.0 | 6.84167E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99425E-07 | 0 | 0 |
| R/Q | rs397517800  |
-0.224 | 0.01 | N | 0.095 | 0.04 | 0.0666544352282 | gnomAD-2.1.1 | 4.01E-05 | None | None | None | None | N | None | 0 | 2.02852E-04 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| R/Q | rs397517800 |
-0.224 | 0.01 | N | 0.095 | 0.04 | 0.0666544352282 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 1.96309E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07211E-04 | 0 |
| R/Q | rs397517800 |
-0.224 | 0.01 | N | 0.095 | 0.04 | 0.0666544352282 | gnomAD-4.0.0 | 3.03636E-05 | None | None | None | None | N | None | 0 | 2.66649E-04 | None | 0 | 4.45494E-05 | None | 0 | 0 | 1.69512E-05 | 8.78387E-05 | 4.80277E-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 | 0.4831 | ambiguous | 0.4938 | ambiguous | -0.686 | Destabilizing | 0.036 | N | 0.21 | neutral | None | None | None | None | N |
| R/C | 0.2392 | likely_benign | 0.2701 | benign | -0.589 | Destabilizing | 0.001 | N | 0.181 | neutral | None | None | None | None | N |
| R/D | 0.7769 | likely_pathogenic | 0.7901 | pathogenic | -0.258 | Destabilizing | 0.148 | N | 0.426 | neutral | None | None | None | None | N |
| R/E | 0.414 | ambiguous | 0.4253 | ambiguous | -0.179 | Destabilizing | 0.08 | N | 0.208 | neutral | None | None | None | None | N |
| R/F | 0.6638 | likely_pathogenic | 0.6712 | pathogenic | -0.8 | Destabilizing | 0.296 | N | 0.501 | neutral | None | None | None | None | N |
| R/G | 0.3033 | likely_benign | 0.3175 | benign | -0.944 | Destabilizing | 0.249 | N | 0.31 | neutral | N | 0.520861038 | None | None | N |
| R/H | 0.1201 | likely_benign | 0.1238 | benign | -1.284 | Destabilizing | 0.001 | N | 0.128 | neutral | None | None | None | None | N |
| R/I | 0.34 | ambiguous | 0.3356 | benign | -0.014 | Destabilizing | 0.001 | N | 0.176 | neutral | None | None | None | None | N |
| R/K | 0.1139 | likely_benign | 0.1124 | benign | -0.778 | Destabilizing | 0.001 | N | 0.101 | neutral | None | None | None | None | N |
| R/L | 0.3276 | likely_benign | 0.3372 | benign | -0.014 | Destabilizing | 0.068 | N | 0.255 | neutral | N | 0.423910494 | None | None | N |
| R/M | 0.377 | ambiguous | 0.3805 | ambiguous | -0.141 | Destabilizing | 0.596 | D | 0.334 | neutral | None | None | None | None | N |
| R/N | 0.6497 | likely_pathogenic | 0.6533 | pathogenic | -0.17 | Destabilizing | 0.148 | N | 0.24 | neutral | None | None | None | None | N |
| R/P | 0.7799 | likely_pathogenic | 0.8074 | pathogenic | -0.218 | Destabilizing | 0.62 | D | 0.463 | neutral | N | 0.468432062 | None | None | N |
| R/Q | 0.1033 | likely_benign | 0.105 | benign | -0.45 | Destabilizing | 0.01 | N | 0.095 | neutral | N | 0.441205389 | None | None | N |
| R/S | 0.531 | ambiguous | 0.5445 | ambiguous | -0.85 | Destabilizing | 0.08 | N | 0.302 | neutral | None | None | None | None | N |
| R/T | 0.3022 | likely_benign | 0.2995 | benign | -0.617 | Destabilizing | 0.148 | N | 0.299 | neutral | None | None | None | None | N |
| R/V | 0.4751 | ambiguous | 0.4754 | ambiguous | -0.218 | Destabilizing | 0.036 | N | 0.343 | neutral | None | None | None | None | N |
| R/W | 0.2111 | likely_benign | 0.2267 | benign | -0.543 | Destabilizing | 0.001 | N | 0.219 | neutral | None | None | None | None | N |
| R/Y | 0.503 | ambiguous | 0.525 | ambiguous | -0.203 | Destabilizing | 0.296 | N | 0.483 | 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.