Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21293 | 64102;64103;64104 | chr2:178587334;178587333;178587332 | chr2:179452061;179452060;179452059 |
| N2AB | 19652 | 59179;59180;59181 | chr2:178587334;178587333;178587332 | chr2:179452061;179452060;179452059 |
| N2A | 18725 | 56398;56399;56400 | chr2:178587334;178587333;178587332 | chr2:179452061;179452060;179452059 |
| N2B | 12228 | 36907;36908;36909 | chr2:178587334;178587333;178587332 | chr2:179452061;179452060;179452059 |
| Novex-1 | 12353 | 37282;37283;37284 | chr2:178587334;178587333;178587332 | chr2:179452061;179452060;179452059 |
| Novex-2 | 12420 | 37483;37484;37485 | chr2:178587334;178587333;178587332 | chr2:179452061;179452060;179452059 |
| 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/E | rs200463088  |
-0.538 | 1.0 | N | 0.445 | 0.376 | 0.304108284078 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 1.16537E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs200463088 |
-0.538 | 1.0 | N | 0.445 | 0.376 | 0.304108284078 | gnomAD-4.0.0 | 6.8466E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65826E-05 |
| D/G | rs747240914 |
-0.754 | 1.0 | N | 0.723 | 0.552 | 0.453024522228 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| D/G | rs747240914 |
-0.754 | 1.0 | N | 0.723 | 0.552 | 0.453024522228 | gnomAD-4.0.0 | 2.73845E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69926E-06 | 0 | 1.6581E-05 |
| D/N | rs199505416 |
-0.147 | 1.0 | N | 0.709 | 0.38 | None | gnomAD-2.1.1 | 7.7E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 4.66E-05 | 1.34621E-04 | 3.34225E-04 |
| D/N | rs199505416 |
-0.147 | 1.0 | N | 0.709 | 0.38 | None | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | N | None | 2.41E-05 | 1.31148E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.17737E-04 | 0 | 0 |
| D/N | rs199505416 |
-0.147 | 1.0 | N | 0.709 | 0.38 | None | gnomAD-4.0.0 | 1.12854E-04 | None | None | None | None | N | None | 1.33383E-05 | 6.6778E-05 | None | 0 | 0 | None | 4.69175E-05 | 0 | 1.38216E-04 | 0 | 1.76237E-04 |
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 | 0.8151 | likely_pathogenic | 0.8748 | pathogenic | -0.112 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.489272457 | None | None | N |
| D/C | 0.9491 | likely_pathogenic | 0.9671 | pathogenic | 0.281 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| D/E | 0.6764 | likely_pathogenic | 0.7591 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.445 | neutral | N | 0.481510549 | None | None | N |
| D/F | 0.973 | likely_pathogenic | 0.9816 | pathogenic | -0.527 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| D/G | 0.8002 | likely_pathogenic | 0.8501 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.49342674 | None | None | N |
| D/H | 0.87 | likely_pathogenic | 0.9018 | pathogenic | -0.874 | Destabilizing | 1.0 | D | 0.652 | neutral | N | 0.507314259 | None | None | N |
| D/I | 0.9254 | likely_pathogenic | 0.9486 | pathogenic | 0.434 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/K | 0.9552 | likely_pathogenic | 0.9664 | pathogenic | 0.274 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/L | 0.9252 | likely_pathogenic | 0.9467 | pathogenic | 0.434 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/M | 0.9671 | likely_pathogenic | 0.9793 | pathogenic | 0.86 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| D/N | 0.2001 | likely_benign | 0.2493 | benign | 0.049 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.470105018 | None | None | N |
| D/P | 0.9746 | likely_pathogenic | 0.9818 | pathogenic | 0.276 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| D/Q | 0.9215 | likely_pathogenic | 0.9437 | pathogenic | 0.08 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/R | 0.9492 | likely_pathogenic | 0.9611 | pathogenic | 0.093 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/S | 0.4917 | ambiguous | 0.5726 | pathogenic | -0.069 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| D/T | 0.7135 | likely_pathogenic | 0.7622 | pathogenic | 0.111 | Stabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| D/V | 0.8507 | likely_pathogenic | 0.8949 | pathogenic | 0.276 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | N | 0.500882252 | None | None | N |
| D/W | 0.9941 | likely_pathogenic | 0.9952 | pathogenic | -0.593 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| D/Y | 0.8377 | likely_pathogenic | 0.8725 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.632 | neutral | N | 0.521899795 | 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.