Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23567 | 70924;70925;70926 | chr2:178575433;178575432;178575431 | chr2:179440160;179440159;179440158 |
| N2AB | 21926 | 66001;66002;66003 | chr2:178575433;178575432;178575431 | chr2:179440160;179440159;179440158 |
| N2A | 20999 | 63220;63221;63222 | chr2:178575433;178575432;178575431 | chr2:179440160;179440159;179440158 |
| N2B | 14502 | 43729;43730;43731 | chr2:178575433;178575432;178575431 | chr2:179440160;179440159;179440158 |
| Novex-1 | 14627 | 44104;44105;44106 | chr2:178575433;178575432;178575431 | chr2:179440160;179440159;179440158 |
| Novex-2 | 14694 | 44305;44306;44307 | chr2:178575433;178575432;178575431 | chr2:179440160;179440159;179440158 |
| 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 | rs1004548694  |
-1.719 | 1.0 | D | 0.867 | 0.838 | 0.882396184161 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| Y/C | rs1004548694 |
-1.719 | 1.0 | D | 0.867 | 0.838 | 0.882396184161 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/C | rs1004548694 |
-1.719 | 1.0 | D | 0.867 | 0.838 | 0.882396184161 | gnomAD-4.0.0 | 1.85931E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69544E-06 | 0 | 1.60143E-05 |
| Y/S | rs1004548694 |
None | 1.0 | D | 0.897 | 0.855 | 0.919593144702 | gnomAD-4.0.0 | 1.36859E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73551E-04 | 8.99575E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9977 | likely_pathogenic | 0.9978 | pathogenic | -2.986 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| Y/C | 0.9552 | likely_pathogenic | 0.9518 | pathogenic | -1.55 | Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.666513903 | None | None | N |
| Y/D | 0.9963 | likely_pathogenic | 0.9968 | pathogenic | -3.622 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | D | 0.666715707 | None | None | N |
| Y/E | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -3.392 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| Y/F | 0.3337 | likely_benign | 0.2893 | benign | -1.155 | Destabilizing | 0.999 | D | 0.645 | neutral | D | 0.574628498 | None | None | N |
| Y/G | 0.9937 | likely_pathogenic | 0.9946 | pathogenic | -3.412 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| Y/H | 0.9874 | likely_pathogenic | 0.9855 | pathogenic | -2.309 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.666110294 | None | None | N |
| Y/I | 0.9829 | likely_pathogenic | 0.9818 | pathogenic | -1.553 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| Y/K | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -2.261 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| Y/L | 0.966 | likely_pathogenic | 0.9664 | pathogenic | -1.553 | Destabilizing | 0.998 | D | 0.775 | deleterious | None | None | None | None | N |
| Y/M | 0.9879 | likely_pathogenic | 0.9873 | pathogenic | -1.248 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| Y/N | 0.9805 | likely_pathogenic | 0.9832 | pathogenic | -3.175 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.666513903 | None | None | N |
| Y/P | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.049 | Highly Destabilizing | 1.0 | D | 0.936 | deleterious | None | None | None | None | N |
| Y/Q | 0.999 | likely_pathogenic | 0.9989 | pathogenic | -2.841 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| Y/R | 0.9967 | likely_pathogenic | 0.9967 | pathogenic | -2.213 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| Y/S | 0.9914 | likely_pathogenic | 0.9923 | pathogenic | -3.423 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.666513903 | None | None | N |
| Y/T | 0.9967 | likely_pathogenic | 0.997 | pathogenic | -3.064 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| Y/V | 0.9711 | likely_pathogenic | 0.9706 | pathogenic | -2.049 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| Y/W | 0.8677 | likely_pathogenic | 0.8583 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.795 | 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.