Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25579 | 76960;76961;76962 | chr2:178569397;178569396;178569395 | chr2:179434124;179434123;179434122 |
| N2AB | 23938 | 72037;72038;72039 | chr2:178569397;178569396;178569395 | chr2:179434124;179434123;179434122 |
| N2A | 23011 | 69256;69257;69258 | chr2:178569397;178569396;178569395 | chr2:179434124;179434123;179434122 |
| N2B | 16514 | 49765;49766;49767 | chr2:178569397;178569396;178569395 | chr2:179434124;179434123;179434122 |
| Novex-1 | 16639 | 50140;50141;50142 | chr2:178569397;178569396;178569395 | chr2:179434124;179434123;179434122 |
| Novex-2 | 16706 | 50341;50342;50343 | chr2:178569397;178569396;178569395 | chr2:179434124;179434123;179434122 |
| 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 | rs1707280961  |
None | 1.0 | D | 0.829 | 0.871 | 0.80865110737 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs1707280961 |
None | 1.0 | D | 0.829 | 0.871 | 0.80865110737 | gnomAD-4.0.0 | 5.07512E-06 | None | None | None | None | N | None | 5.24347E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20495E-06 | 0 | 3.40252E-05 |
| Y/H | rs1254023475 |
-1.824 | 1.0 | D | 0.802 | 0.88 | 0.675001386424 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs1254023475 |
-1.824 | 1.0 | D | 0.802 | 0.88 | 0.675001386424 | gnomAD-4.0.0 | 1.36877E-06 | None | None | None | None | N | None | 0 | 2.23734E-05 | None | 0 | 0 | None | 0 | 0 | 8.99616E-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 | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -2.571 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| Y/C | 0.9834 | likely_pathogenic | 0.9864 | pathogenic | -1.904 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.629974766 | None | None | N |
| Y/D | 0.9987 | likely_pathogenic | 0.9988 | pathogenic | -3.01 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.646226292 | None | None | N |
| Y/E | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -2.753 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| Y/F | 0.2798 | likely_benign | 0.2869 | benign | -0.939 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | D | 0.592930221 | None | None | N |
| Y/G | 0.9972 | likely_pathogenic | 0.9974 | pathogenic | -3.041 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| Y/H | 0.9892 | likely_pathogenic | 0.9905 | pathogenic | -2.263 | Highly Destabilizing | 1.0 | D | 0.802 | deleterious | D | 0.646024487 | None | None | N |
| Y/I | 0.9686 | likely_pathogenic | 0.9729 | pathogenic | -1.013 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| Y/K | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.145 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| Y/L | 0.945 | likely_pathogenic | 0.9474 | pathogenic | -1.013 | Destabilizing | 0.999 | D | 0.782 | deleterious | None | None | None | None | N |
| Y/M | 0.9877 | likely_pathogenic | 0.9887 | pathogenic | -1.085 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| Y/N | 0.9927 | likely_pathogenic | 0.9935 | pathogenic | -3.07 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | D | 0.646226292 | None | None | N |
| Y/P | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -1.55 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| Y/Q | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -2.603 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| Y/R | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | -2.365 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| Y/S | 0.9978 | likely_pathogenic | 0.998 | pathogenic | -3.43 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.646226292 | None | None | N |
| Y/T | 0.999 | likely_pathogenic | 0.999 | pathogenic | -3.022 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| Y/V | 0.9681 | likely_pathogenic | 0.971 | pathogenic | -1.55 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| Y/W | 0.8963 | likely_pathogenic | 0.9021 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.793 | 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.