Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16471 | 49636;49637;49638 | chr2:178613872;178613871;178613870 | chr2:179478599;179478598;179478597 |
| N2AB | 14830 | 44713;44714;44715 | chr2:178613872;178613871;178613870 | chr2:179478599;179478598;179478597 |
| N2A | 13903 | 41932;41933;41934 | chr2:178613872;178613871;178613870 | chr2:179478599;179478598;179478597 |
| N2B | 7406 | 22441;22442;22443 | chr2:178613872;178613871;178613870 | chr2:179478599;179478598;179478597 |
| Novex-1 | 7531 | 22816;22817;22818 | chr2:178613872;178613871;178613870 | chr2:179478599;179478598;179478597 |
| Novex-2 | 7598 | 23017;23018;23019 | chr2:178613872;178613871;178613870 | chr2:179478599;179478598;179478597 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | rs202094100  |
-1.763 | 1.0 | D | 0.859 | 0.74 | 0.906534809592 | gnomAD-2.1.1 | 3.877E-04 | None | None | None | None | N | None | 4.14E-05 | 1.4228E-04 | None | 9.74E-05 | 0 | None | 0 | None | 4.82664E-04 | 6.51481E-04 | 8.47218E-04 |
| W/C | rs202094100 |
-1.763 | 1.0 | D | 0.859 | 0.74 | 0.906534809592 | gnomAD-3.1.2 | 3.75217E-04 | None | None | None | None | N | None | 9.66E-05 | 1.31354E-04 | 0 | 0 | 0 | None | 3.77003E-04 | 0 | 6.91868E-04 | 0 | 0 |
| W/C | rs202094100 |
-1.763 | 1.0 | D | 0.859 | 0.74 | 0.906534809592 |
Rees (2021)
| None |
MmD 
|
comp het with R17337* | None | None | N | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Domain unfolded in vitro (Tm 32 degrees lower than WT) | None | None | None | None | None | None | None | None | None | None | None |
| W/C | rs202094100 |
-1.763 | 1.0 | D | 0.859 | 0.74 | 0.906534809592 | gnomAD-4.0.0 | 6.85013E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00163E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.998 | likely_pathogenic | 0.9982 | pathogenic | -3.716 | Highly Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| W/C | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -2.272 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.816325836 | None | None | N |
| W/D | 0.9998 | likely_pathogenic | 0.9999 | pathogenic | -3.928 | Highly Destabilizing | 1.0 | D | 0.922 | deleterious | None | None | None | None | N |
| W/E | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.82 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| W/F | 0.8082 | likely_pathogenic | 0.8024 | pathogenic | -2.332 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| W/G | 0.9902 | likely_pathogenic | 0.9904 | pathogenic | -3.951 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.816325836 | None | None | N |
| W/H | 0.9989 | likely_pathogenic | 0.9988 | pathogenic | -2.847 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| W/I | 0.9961 | likely_pathogenic | 0.9967 | pathogenic | -2.791 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| W/K | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -2.862 | Highly Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| W/L | 0.991 | likely_pathogenic | 0.9911 | pathogenic | -2.791 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.817469194 | None | None | N |
| W/M | 0.9983 | likely_pathogenic | 0.9984 | pathogenic | -2.288 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| W/N | 0.9998 | likely_pathogenic | 0.9999 | pathogenic | -3.521 | Highly Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | None | N |
| W/P | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -3.132 | Highly Destabilizing | 1.0 | D | 0.935 | deleterious | None | None | None | None | N |
| W/Q | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.408 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| W/R | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -2.422 | Highly Destabilizing | 1.0 | D | 0.922 | deleterious | D | 0.816325836 | None | None | N |
| W/S | 0.9973 | likely_pathogenic | 0.9977 | pathogenic | -3.701 | Highly Destabilizing | 1.0 | D | 0.904 | deleterious | D | 0.784491204 | None | None | N |
| W/T | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -3.518 | Highly Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| W/V | 0.996 | likely_pathogenic | 0.9962 | pathogenic | -3.132 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | N |
| W/Y | 0.9685 | likely_pathogenic | 0.9662 | pathogenic | -2.228 | Highly Destabilizing | 1.0 | D | 0.839 | 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.