Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35898 | 107917;107918;107919 | chr2:178527296;178527295;178527294 | chr2:179392023;179392022;179392021 |
| N2AB | 34257 | 102994;102995;102996 | chr2:178527296;178527295;178527294 | chr2:179392023;179392022;179392021 |
| N2A | 33330 | 100213;100214;100215 | chr2:178527296;178527295;178527294 | chr2:179392023;179392022;179392021 |
| N2B | 26833 | 80722;80723;80724 | chr2:178527296;178527295;178527294 | chr2:179392023;179392022;179392021 |
| Novex-1 | 26958 | 81097;81098;81099 | chr2:178527296;178527295;178527294 | chr2:179392023;179392022;179392021 |
| Novex-2 | 27025 | 81298;81299;81300 | chr2:178527296;178527295;178527294 | chr2:179392023;179392022;179392021 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs1028436080  |
0.38 | 0.98 | N | 0.347 | 0.358 | 0.391156786388 | gnomAD-2.1.1 | 1.28E-05 | None | None | None | 0.239(OBSL1) 0.049(OBSCN) | N | None | 0 | 9.58E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/E | rs1028436080 |
0.38 | 0.98 | N | 0.347 | 0.358 | 0.391156786388 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | 0.239(OBSL1) 0.049(OBSCN) | N | None | 0 | 1.30924E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/E | rs1028436080 |
0.38 | 0.98 | N | 0.347 | 0.358 | 0.391156786388 | gnomAD-4.0.0 | 7.88915E-06 | None | None | None | 0.239(OBSL1) 0.049(OBSCN) | N | None | 0 | 7.13903E-05 | None | 0 | 0 | None | 0 | 0 | 4.90964E-06 | 0 | 0 |
| K/I | rs774242716 |
0.747 | 0.999 | D | 0.65 | 0.482 | 0.494500980894 | gnomAD-2.1.1 | 1.89E-05 | None | None | None | 0.654(OBSL1) -0.253(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.63733E-04 | 8.15E-06 | 0 |
| K/I | rs774242716 |
0.747 | 0.999 | D | 0.65 | 0.482 | 0.494500980894 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | 0.654(OBSL1) -0.253(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88253E-04 | 0 | 0 | 0 | 0 |
| K/I | rs774242716 |
0.747 | 0.999 | D | 0.65 | 0.482 | 0.494500980894 | gnomAD-4.0.0 | 2.23475E-05 | None | None | None | 0.654(OBSL1) -0.253(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 1.89358E-04 | 0 | 9.81769E-06 | 0 | 2.92672E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6714 | likely_pathogenic | 0.6771 | pathogenic | -0.215 | Destabilizing | 0.993 | D | 0.373 | neutral | None | None | None | 0.678(OBSL1) -0.232(OBSCN) | N |
| K/C | 0.8916 | likely_pathogenic | 0.906 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | 0.293(OBSL1) 0.252(OBSCN) | N |
| K/D | 0.9097 | likely_pathogenic | 0.9087 | pathogenic | 0.107 | Stabilizing | 0.998 | D | 0.455 | neutral | None | None | None | 0.311(OBSL1) 0.086(OBSCN) | N |
| K/E | 0.373 | ambiguous | 0.3779 | ambiguous | 0.179 | Stabilizing | 0.98 | D | 0.347 | neutral | N | 0.508585174 | None | 0.239(OBSL1) 0.049(OBSCN) | N |
| K/F | 0.9545 | likely_pathogenic | 0.9545 | pathogenic | -0.07 | Destabilizing | 0.999 | D | 0.662 | neutral | None | None | None | 0.753(OBSL1) 0.059(OBSCN) | N |
| K/G | 0.838 | likely_pathogenic | 0.8332 | pathogenic | -0.523 | Destabilizing | 0.993 | D | 0.425 | neutral | None | None | None | 0.659(OBSL1) -0.227(OBSCN) | N |
| K/H | 0.5696 | likely_pathogenic | 0.5946 | pathogenic | -0.787 | Destabilizing | 0.999 | D | 0.496 | neutral | None | None | None | 0.703(OBSL1) 0.146(OBSCN) | N |
| K/I | 0.6243 | likely_pathogenic | 0.6436 | pathogenic | 0.548 | Stabilizing | 0.999 | D | 0.65 | neutral | D | 0.529520594 | None | 0.654(OBSL1) -0.253(OBSCN) | N |
| K/L | 0.7088 | likely_pathogenic | 0.7092 | pathogenic | 0.548 | Stabilizing | 0.993 | D | 0.425 | neutral | None | None | None | 0.654(OBSL1) -0.253(OBSCN) | N |
| K/M | 0.4966 | ambiguous | 0.5104 | ambiguous | 0.278 | Stabilizing | 1.0 | D | 0.493 | neutral | None | None | None | 0.715(OBSL1) 0.434(OBSCN) | N |
| K/N | 0.7683 | likely_pathogenic | 0.7722 | pathogenic | -0.079 | Destabilizing | 0.997 | D | 0.354 | neutral | N | 0.50287271 | None | 0.831(OBSL1) -0.436(OBSCN) | N |
| K/P | 0.9837 | likely_pathogenic | 0.9812 | pathogenic | 0.324 | Stabilizing | 0.999 | D | 0.491 | neutral | None | None | None | 0.676(OBSL1) -0.245(OBSCN) | N |
| K/Q | 0.2333 | likely_benign | 0.2484 | benign | -0.164 | Destabilizing | 0.994 | D | 0.378 | neutral | N | 0.496618741 | None | 0.846(OBSL1) -0.235(OBSCN) | N |
| K/R | 0.1013 | likely_benign | 0.1061 | benign | -0.293 | Destabilizing | 0.061 | N | 0.127 | neutral | N | 0.456041555 | None | 0.172(OBSL1) -0.583(OBSCN) | N |
| K/S | 0.7498 | likely_pathogenic | 0.7538 | pathogenic | -0.654 | Destabilizing | 0.993 | D | 0.334 | neutral | None | None | None | 0.879(OBSL1) -0.322(OBSCN) | N |
| K/T | 0.3844 | ambiguous | 0.3992 | ambiguous | -0.396 | Destabilizing | 0.99 | D | 0.405 | neutral | N | 0.497773535 | None | 0.828(OBSL1) -0.308(OBSCN) | N |
| K/V | 0.5362 | ambiguous | 0.5588 | ambiguous | 0.324 | Stabilizing | 0.998 | D | 0.512 | neutral | None | None | None | 0.676(OBSL1) -0.245(OBSCN) | N |
| K/W | 0.9604 | likely_pathogenic | 0.9606 | pathogenic | -0.014 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | 0.404(OBSL1) 0.212(OBSCN) | N |
| K/Y | 0.8982 | likely_pathogenic | 0.9023 | pathogenic | 0.291 | Stabilizing | 0.999 | D | 0.614 | neutral | None | None | None | 0.785(OBSL1) 0.162(OBSCN) | 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.