Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17836 | 53731;53732;53733 | chr2:178607096;178607095;178607094 | chr2:179471823;179471822;179471821 |
| N2AB | 16195 | 48808;48809;48810 | chr2:178607096;178607095;178607094 | chr2:179471823;179471822;179471821 |
| N2A | 15268 | 46027;46028;46029 | chr2:178607096;178607095;178607094 | chr2:179471823;179471822;179471821 |
| N2B | 8771 | 26536;26537;26538 | chr2:178607096;178607095;178607094 | chr2:179471823;179471822;179471821 |
| Novex-1 | 8896 | 26911;26912;26913 | chr2:178607096;178607095;178607094 | chr2:179471823;179471822;179471821 |
| Novex-2 | 8963 | 27112;27113;27114 | chr2:178607096;178607095;178607094 | chr2:179471823;179471822;179471821 |
| 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 | rs376153809  |
-1.599 | 1.0 | D | 0.813 | 0.572 | None | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/C | rs376153809 |
-1.599 | 1.0 | D | 0.813 | 0.572 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs376153809 |
-1.599 | 1.0 | D | 0.813 | 0.572 | None | gnomAD-4.0.0 | 1.98475E-05 | None | None | None | None | N | None | 0 | 1.66973E-05 | None | 0 | 0 | None | 0 | 0 | 2.54421E-05 | 0 | 1.60272E-05 |
| R/H | rs373526624 |
-2.282 | 1.0 | D | 0.824 | 0.625 | None | gnomAD-2.1.1 | 6.26908E-04 | None | None | None | None | N | None | 2.89783E-04 | 5.68E-05 | None | 0 | 1.03295E-04 | None | 5.10339E-03 | None | 0 | 4.7E-05 | 4.22297E-04 |
| R/H | rs373526624 |
-2.282 | 1.0 | D | 0.824 | 0.625 | None | gnomAD-3.1.2 | 1.97423E-04 | None | None | None | None | N | None | 1.93237E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 4.14594E-03 | 0 |
| R/H | rs373526624 |
-2.282 | 1.0 | D | 0.824 | 0.625 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 5.1E-03 | None |
| R/H | rs373526624 |
-2.282 | 1.0 | D | 0.824 | 0.625 | None | gnomAD-4.0.0 | 3.1876E-04 | None | None | None | None | N | None | 2.40301E-04 | 6.67579E-05 | None | 0 | 8.94294E-05 | None | 0 | 3.30688E-04 | 3.73148E-05 | 4.65746E-03 | 3.0438E-04 |
| R/S | rs376153809 |
None | 1.0 | D | 0.746 | 0.549 | 0.485562757867 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs376153809 |
None | 1.0 | D | 0.746 | 0.549 | 0.485562757867 | gnomAD-4.0.0 | 6.58345E-06 | None | None | None | None | N | None | 2.41639E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.985 | likely_pathogenic | 0.9802 | pathogenic | -1.76 | Destabilizing | 0.999 | D | 0.618 | neutral | None | None | None | None | N |
| R/C | 0.7983 | likely_pathogenic | 0.7373 | pathogenic | -1.743 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.526093759 | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.9977 | pathogenic | -1.155 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| R/E | 0.9827 | likely_pathogenic | 0.9729 | pathogenic | -0.934 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| R/F | 0.9965 | likely_pathogenic | 0.9931 | pathogenic | -0.782 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| R/G | 0.9867 | likely_pathogenic | 0.9813 | pathogenic | -2.099 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.537361159 | None | None | N |
| R/H | 0.7764 | likely_pathogenic | 0.7025 | pathogenic | -1.886 | Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.537614648 | None | None | N |
| R/I | 0.9748 | likely_pathogenic | 0.9525 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| R/K | 0.6961 | likely_pathogenic | 0.6475 | pathogenic | -1.303 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | N |
| R/L | 0.9611 | likely_pathogenic | 0.9432 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.526093759 | None | None | N |
| R/M | 0.9821 | likely_pathogenic | 0.9699 | pathogenic | -1.335 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| R/N | 0.9943 | likely_pathogenic | 0.9917 | pathogenic | -1.5 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| R/P | 0.9996 | likely_pathogenic | 0.9992 | pathogenic | -1.091 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.537868138 | None | None | N |
| R/Q | 0.6679 | likely_pathogenic | 0.5867 | pathogenic | -1.221 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| R/S | 0.9899 | likely_pathogenic | 0.9861 | pathogenic | -2.193 | Highly Destabilizing | 1.0 | D | 0.746 | deleterious | D | 0.522544905 | None | None | N |
| R/T | 0.9852 | likely_pathogenic | 0.9771 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/V | 0.9775 | likely_pathogenic | 0.9603 | pathogenic | -1.091 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| R/W | 0.9464 | likely_pathogenic | 0.9008 | pathogenic | -0.426 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/Y | 0.987 | likely_pathogenic | 0.9775 | pathogenic | -0.301 | Destabilizing | 1.0 | D | 0.829 | deleterious | 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.