Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15833 | 47722;47723;47724 | chr2:178617854;178617853;178617852 | chr2:179482581;179482580;179482579 |
| N2AB | 14192 | 42799;42800;42801 | chr2:178617854;178617853;178617852 | chr2:179482581;179482580;179482579 |
| N2A | 13265 | 40018;40019;40020 | chr2:178617854;178617853;178617852 | chr2:179482581;179482580;179482579 |
| N2B | 6768 | 20527;20528;20529 | chr2:178617854;178617853;178617852 | chr2:179482581;179482580;179482579 |
| Novex-1 | 6893 | 20902;20903;20904 | chr2:178617854;178617853;178617852 | chr2:179482581;179482580;179482579 |
| Novex-2 | 6960 | 21103;21104;21105 | chr2:178617854;178617853;178617852 | chr2:179482581;179482580;179482579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs758495958  |
-3.313 | 0.996 | D | 0.88 | 0.893 | 0.906140027571 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66058E-04 |
| V/E | rs758495958 |
-3.313 | 0.996 | D | 0.88 | 0.893 | 0.906140027571 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 6.58E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | rs758495958 |
-3.313 | 0.996 | D | 0.88 | 0.893 | 0.906140027571 | gnomAD-4.0.0 | 5.13286E-06 | None | None | None | None | N | None | 0 | 5.09338E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.85128E-05 |
| V/M | None | None | 0.978 | D | 0.825 | 0.642 | 0.704055910078 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.874 | likely_pathogenic | 0.894 | pathogenic | -2.697 | Highly Destabilizing | 0.928 | D | 0.681 | prob.neutral | D | 0.767261197 | None | None | N |
| V/C | 0.9685 | likely_pathogenic | 0.9665 | pathogenic | -2.115 | Highly Destabilizing | 0.999 | D | 0.825 | deleterious | None | None | None | None | N |
| V/D | 0.9988 | likely_pathogenic | 0.9988 | pathogenic | -3.538 | Highly Destabilizing | 0.997 | D | 0.897 | deleterious | None | None | None | None | N |
| V/E | 0.9958 | likely_pathogenic | 0.9954 | pathogenic | -3.239 | Highly Destabilizing | 0.996 | D | 0.88 | deleterious | D | 0.823007773 | None | None | N |
| V/F | 0.9152 | likely_pathogenic | 0.9384 | pathogenic | -1.461 | Destabilizing | 0.983 | D | 0.853 | deleterious | None | None | None | None | N |
| V/G | 0.9226 | likely_pathogenic | 0.9288 | pathogenic | -3.261 | Highly Destabilizing | 0.989 | D | 0.895 | deleterious | D | 0.823007773 | None | None | N |
| V/H | 0.999 | likely_pathogenic | 0.9991 | pathogenic | -2.979 | Highly Destabilizing | 0.999 | D | 0.874 | deleterious | None | None | None | None | N |
| V/I | 0.1379 | likely_benign | 0.1339 | benign | -1.045 | Destabilizing | 0.05 | N | 0.335 | neutral | None | None | None | None | N |
| V/K | 0.9971 | likely_pathogenic | 0.9971 | pathogenic | -2.159 | Highly Destabilizing | 0.992 | D | 0.882 | deleterious | None | None | None | None | N |
| V/L | 0.7349 | likely_pathogenic | 0.738 | pathogenic | -1.045 | Destabilizing | 0.476 | N | 0.647 | neutral | D | 0.661667575 | None | None | N |
| V/M | 0.8666 | likely_pathogenic | 0.8671 | pathogenic | -1.342 | Destabilizing | 0.978 | D | 0.825 | deleterious | D | 0.723191661 | None | None | N |
| V/N | 0.996 | likely_pathogenic | 0.9954 | pathogenic | -2.774 | Highly Destabilizing | 0.997 | D | 0.902 | deleterious | None | None | None | None | N |
| V/P | 0.9952 | likely_pathogenic | 0.9959 | pathogenic | -1.58 | Destabilizing | 0.997 | D | 0.89 | deleterious | None | None | None | None | N |
| V/Q | 0.9945 | likely_pathogenic | 0.9948 | pathogenic | -2.455 | Highly Destabilizing | 0.997 | D | 0.895 | deleterious | None | None | None | None | N |
| V/R | 0.992 | likely_pathogenic | 0.9929 | pathogenic | -2.114 | Highly Destabilizing | 0.997 | D | 0.903 | deleterious | None | None | None | None | N |
| V/S | 0.9764 | likely_pathogenic | 0.977 | pathogenic | -3.278 | Highly Destabilizing | 0.992 | D | 0.886 | deleterious | None | None | None | None | N |
| V/T | 0.9459 | likely_pathogenic | 0.9429 | pathogenic | -2.839 | Highly Destabilizing | 0.944 | D | 0.758 | deleterious | None | None | None | None | N |
| V/W | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -1.998 | Destabilizing | 0.999 | D | 0.859 | deleterious | None | None | None | None | N |
| V/Y | 0.9939 | likely_pathogenic | 0.9956 | pathogenic | -1.773 | Destabilizing | 0.992 | D | 0.857 | 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.