Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22130 | 66613;66614;66615 | chr2:178581981;178581980;178581979 | chr2:179446708;179446707;179446706 |
| N2AB | 20489 | 61690;61691;61692 | chr2:178581981;178581980;178581979 | chr2:179446708;179446707;179446706 |
| N2A | 19562 | 58909;58910;58911 | chr2:178581981;178581980;178581979 | chr2:179446708;179446707;179446706 |
| N2B | 13065 | 39418;39419;39420 | chr2:178581981;178581980;178581979 | chr2:179446708;179446707;179446706 |
| Novex-1 | 13190 | 39793;39794;39795 | chr2:178581981;178581980;178581979 | chr2:179446708;179446707;179446706 |
| Novex-2 | 13257 | 39994;39995;39996 | chr2:178581981;178581980;178581979 | chr2:179446708;179446707;179446706 |
| 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/I | rs1227757855  |
None | 0.997 | N | 0.572 | 0.483 | 0.694280915357 | gnomAD-4.0.0 | 1.36881E-06 | None | None | None | None | N | None | 2.9915E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65728E-05 |
| V/L | rs1227757855 |
-0.09 | 0.997 | N | 0.676 | 0.653 | 0.756346533954 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11907E-04 | None | 0 | None | 0 | 2.67E-05 | 1.65893E-04 |
| V/L | rs1227757855 |
-0.09 | 0.997 | N | 0.676 | 0.653 | 0.756346533954 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9425E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs1227757855 |
-0.09 | 0.997 | N | 0.676 | 0.653 | 0.756346533954 | gnomAD-4.0.0 | 1.36375E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.56362E-04 | None | 0 | 0 | 1.01737E-05 | 0 | 4.80523E-05 |
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 | 0.718 | likely_pathogenic | 0.6995 | pathogenic | -2.255 | Highly Destabilizing | 0.999 | D | 0.673 | neutral | D | 0.542110641 | None | None | N |
| V/C | 0.9474 | likely_pathogenic | 0.942 | pathogenic | -2.164 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| V/D | 0.9987 | likely_pathogenic | 0.9982 | pathogenic | -3.315 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | D | 0.644574368 | None | None | N |
| V/E | 0.9965 | likely_pathogenic | 0.9954 | pathogenic | -3.043 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| V/F | 0.9732 | likely_pathogenic | 0.9612 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.566962845 | None | None | N |
| V/G | 0.92 | likely_pathogenic | 0.9011 | pathogenic | -2.816 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | D | 0.644574368 | None | None | N |
| V/H | 0.9993 | likely_pathogenic | 0.9989 | pathogenic | -2.616 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/I | 0.1552 | likely_benign | 0.1541 | benign | -0.645 | Destabilizing | 0.997 | D | 0.572 | neutral | N | 0.49838635 | None | None | N |
| V/K | 0.9981 | likely_pathogenic | 0.9972 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| V/L | 0.8532 | likely_pathogenic | 0.8284 | pathogenic | -0.645 | Destabilizing | 0.997 | D | 0.676 | prob.neutral | N | 0.517646375 | None | None | N |
| V/M | 0.9007 | likely_pathogenic | 0.8791 | pathogenic | -1.147 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| V/N | 0.9933 | likely_pathogenic | 0.9915 | pathogenic | -2.331 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| V/P | 0.9964 | likely_pathogenic | 0.9959 | pathogenic | -1.161 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| V/Q | 0.9956 | likely_pathogenic | 0.994 | pathogenic | -2.058 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| V/R | 0.9952 | likely_pathogenic | 0.9935 | pathogenic | -1.776 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| V/S | 0.9534 | likely_pathogenic | 0.9493 | pathogenic | -2.858 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| V/T | 0.9111 | likely_pathogenic | 0.9043 | pathogenic | -2.44 | Highly Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| V/W | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.692 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| V/Y | 0.997 | likely_pathogenic | 0.9956 | pathogenic | -1.391 | Destabilizing | 1.0 | D | 0.81 | 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.