Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29375 | 88348;88349;88350 | chr2:178557031;178557030;178557029 | chr2:179421758;179421757;179421756 |
| N2AB | 27734 | 83425;83426;83427 | chr2:178557031;178557030;178557029 | chr2:179421758;179421757;179421756 |
| N2A | 26807 | 80644;80645;80646 | chr2:178557031;178557030;178557029 | chr2:179421758;179421757;179421756 |
| N2B | 20310 | 61153;61154;61155 | chr2:178557031;178557030;178557029 | chr2:179421758;179421757;179421756 |
| Novex-1 | 20435 | 61528;61529;61530 | chr2:178557031;178557030;178557029 | chr2:179421758;179421757;179421756 |
| Novex-2 | 20502 | 61729;61730;61731 | chr2:178557031;178557030;178557029 | chr2:179421758;179421757;179421756 |
| 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/C | rs368439674  |
-1.62 | 0.998 | N | 0.622 | 0.426 | None | gnomAD-2.1.1 | 8.05E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 7.84753E-04 | None | 0 | None | 0 | 4.44E-05 | 0 |
| R/C | rs368439674 |
-1.62 | 0.998 | N | 0.622 | 0.426 | None | gnomAD-3.1.2 | 9.86E-05 | None | None | None | None | N | None | 0 | 6.5505E-04 | 0 | 0 | 1.9253E-04 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/C | rs368439674 |
-1.62 | 0.998 | N | 0.622 | 0.426 | None | gnomAD-4.0.0 | 3.16057E-05 | None | None | None | None | N | None | 1.33472E-05 | 1.8337E-04 | None | 0 | 2.00947E-04 | None | 0 | 1.6442E-04 | 2.28846E-05 | 0 | 3.20225E-05 |
| R/H | rs761246441 |
-2.104 | 0.047 | N | 0.297 | 0.238 | 0.214338557667 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 1.16003E-04 | None | 0 | 1.12108E-04 | None | 0 | None | 0 | 0 | 0 |
| R/H | rs761246441 |
-2.104 | 0.047 | N | 0.297 | 0.238 | 0.214338557667 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88786E-04 | 0 | 0 | 0 | 0 |
| R/H | rs761246441 |
-2.104 | 0.047 | N | 0.297 | 0.238 | 0.214338557667 | gnomAD-4.0.0 | 1.11551E-05 | None | None | None | None | N | None | 2.66987E-05 | 5.00083E-05 | None | 0 | 4.46568E-05 | None | 3.12617E-05 | 0 | 6.78063E-06 | 0 | 1.60118E-05 |
| R/L | rs761246441 |
None | 0.756 | N | 0.535 | 0.317 | 0.457286136841 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | rs761246441 |
None | 0.756 | N | 0.535 | 0.317 | 0.457286136841 | gnomAD-4.0.0 | 6.57289E-06 | None | None | None | None | N | None | 2.41359E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | None | 0.756 | N | 0.452 | 0.351 | 0.330589388543 | gnomAD-4.0.0 | 6.84235E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99441E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9189 | likely_pathogenic | 0.839 | pathogenic | -2.065 | Highly Destabilizing | 0.4 | N | 0.476 | neutral | None | None | None | None | N |
| R/C | 0.3844 | ambiguous | 0.2696 | benign | -2.01 | Highly Destabilizing | 0.998 | D | 0.622 | neutral | N | 0.48585587 | None | None | N |
| R/D | 0.9868 | likely_pathogenic | 0.9773 | pathogenic | -0.799 | Destabilizing | 0.617 | D | 0.589 | neutral | None | None | None | None | N |
| R/E | 0.864 | likely_pathogenic | 0.7965 | pathogenic | -0.599 | Destabilizing | 0.447 | N | 0.456 | neutral | None | None | None | None | N |
| R/F | 0.9431 | likely_pathogenic | 0.8869 | pathogenic | -1.442 | Destabilizing | 0.85 | D | 0.593 | neutral | None | None | None | None | N |
| R/G | 0.8367 | likely_pathogenic | 0.7182 | pathogenic | -2.415 | Highly Destabilizing | 0.756 | D | 0.507 | neutral | N | 0.509631664 | None | None | N |
| R/H | 0.2919 | likely_benign | 0.2914 | benign | -2.226 | Highly Destabilizing | 0.047 | N | 0.297 | neutral | N | 0.503555278 | None | None | N |
| R/I | 0.88 | likely_pathogenic | 0.7859 | pathogenic | -1.06 | Destabilizing | 0.92 | D | 0.61 | neutral | None | None | None | None | N |
| R/K | 0.1475 | likely_benign | 0.1214 | benign | -1.532 | Destabilizing | 0.009 | N | 0.143 | neutral | None | None | None | None | N |
| R/L | 0.7127 | likely_pathogenic | 0.5768 | pathogenic | -1.06 | Destabilizing | 0.756 | D | 0.535 | neutral | N | 0.49751489 | None | None | N |
| R/M | 0.7272 | likely_pathogenic | 0.5997 | pathogenic | -1.44 | Destabilizing | 0.992 | D | 0.512 | neutral | None | None | None | None | N |
| R/N | 0.9548 | likely_pathogenic | 0.9191 | pathogenic | -1.31 | Destabilizing | 0.447 | N | 0.463 | neutral | None | None | None | None | N |
| R/P | 0.9967 | likely_pathogenic | 0.9937 | pathogenic | -1.382 | Destabilizing | 0.01 | N | 0.378 | neutral | D | 0.539510298 | None | None | N |
| R/Q | 0.2128 | likely_benign | 0.1636 | benign | -1.326 | Destabilizing | 0.617 | D | 0.507 | neutral | None | None | None | None | N |
| R/S | 0.9549 | likely_pathogenic | 0.9072 | pathogenic | -2.342 | Highly Destabilizing | 0.756 | D | 0.452 | neutral | N | 0.52165518 | None | None | N |
| R/T | 0.8983 | likely_pathogenic | 0.8127 | pathogenic | -1.924 | Destabilizing | 0.766 | D | 0.483 | neutral | None | None | None | None | N |
| R/V | 0.9116 | likely_pathogenic | 0.8306 | pathogenic | -1.382 | Destabilizing | 0.92 | D | 0.603 | neutral | None | None | None | None | N |
| R/W | 0.6157 | likely_pathogenic | 0.4814 | ambiguous | -0.855 | Destabilizing | 0.992 | D | 0.651 | neutral | None | None | None | None | N |
| R/Y | 0.8411 | likely_pathogenic | 0.7446 | pathogenic | -0.719 | Destabilizing | 0.739 | D | 0.605 | 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.