Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25275 | 76048;76049;76050 | chr2:178570309;178570308;178570307 | chr2:179435036;179435035;179435034 |
| N2AB | 23634 | 71125;71126;71127 | chr2:178570309;178570308;178570307 | chr2:179435036;179435035;179435034 |
| N2A | 22707 | 68344;68345;68346 | chr2:178570309;178570308;178570307 | chr2:179435036;179435035;179435034 |
| N2B | 16210 | 48853;48854;48855 | chr2:178570309;178570308;178570307 | chr2:179435036;179435035;179435034 |
| Novex-1 | 16335 | 49228;49229;49230 | chr2:178570309;178570308;178570307 | chr2:179435036;179435035;179435034 |
| Novex-2 | 16402 | 49429;49430;49431 | chr2:178570309;178570308;178570307 | chr2:179435036;179435035;179435034 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 1.0 | D | 0.897 | 0.938 | 0.890550101821 | gnomAD-4.0.0 | 3.18464E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.82393E-04 | 0 | 0 | 0 |
| Y/H | rs1707703238  |
None | 1.0 | D | 0.811 | 0.854 | 0.797076662116 | 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 |
| Y/H | rs1707703238 |
None | 1.0 | D | 0.811 | 0.854 | 0.797076662116 | gnomAD-4.0.0 | 4.05994E-06 | None | None | None | None | N | None | 1.74709E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61485E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9978 | likely_pathogenic | 0.9983 | pathogenic | -3.701 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| Y/C | 0.9818 | likely_pathogenic | 0.9869 | pathogenic | -2.197 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.658309522 | None | None | N |
| Y/D | 0.9941 | likely_pathogenic | 0.9951 | pathogenic | -3.774 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | D | 0.690580408 | None | None | N |
| Y/E | 0.9989 | likely_pathogenic | 0.9991 | pathogenic | -3.597 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| Y/F | 0.6583 | likely_pathogenic | 0.7103 | pathogenic | -1.472 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | D | 0.643492063 | None | None | N |
| Y/G | 0.9894 | likely_pathogenic | 0.9902 | pathogenic | -4.067 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| Y/H | 0.9925 | likely_pathogenic | 0.9949 | pathogenic | -2.452 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.690580408 | None | None | N |
| Y/I | 0.983 | likely_pathogenic | 0.9867 | pathogenic | -2.467 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| Y/K | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -2.422 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| Y/L | 0.9697 | likely_pathogenic | 0.974 | pathogenic | -2.467 | Highly Destabilizing | 0.999 | D | 0.812 | deleterious | None | None | None | None | N |
| Y/M | 0.9907 | likely_pathogenic | 0.9927 | pathogenic | -2.234 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| Y/N | 0.9708 | likely_pathogenic | 0.9775 | pathogenic | -3.047 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | D | 0.690378604 | None | None | N |
| Y/P | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -2.894 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| Y/Q | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -2.913 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| Y/R | 0.9978 | likely_pathogenic | 0.9982 | pathogenic | -1.931 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| Y/S | 0.9922 | likely_pathogenic | 0.9938 | pathogenic | -3.423 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | D | 0.674328883 | None | None | N |
| Y/T | 0.9967 | likely_pathogenic | 0.9973 | pathogenic | -3.142 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| Y/V | 0.9654 | likely_pathogenic | 0.9715 | pathogenic | -2.894 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| Y/W | 0.9557 | likely_pathogenic | 0.9675 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.797 | 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.