Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21373 | 64342;64343;64344 | chr2:178586784;178586783;178586782 | chr2:179451511;179451510;179451509 |
| N2AB | 19732 | 59419;59420;59421 | chr2:178586784;178586783;178586782 | chr2:179451511;179451510;179451509 |
| N2A | 18805 | 56638;56639;56640 | chr2:178586784;178586783;178586782 | chr2:179451511;179451510;179451509 |
| N2B | 12308 | 37147;37148;37149 | chr2:178586784;178586783;178586782 | chr2:179451511;179451510;179451509 |
| Novex-1 | 12433 | 37522;37523;37524 | chr2:178586784;178586783;178586782 | chr2:179451511;179451510;179451509 |
| Novex-2 | 12500 | 37723;37724;37725 | chr2:178586784;178586783;178586782 | chr2:179451511;179451510;179451509 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs753245626  |
-1.892 | 0.942 | N | 0.746 | 0.314 | 0.305730143919 | gnomAD-2.1.1 | 4.04E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27955E-04 | None | 0 | 0 | 0 |
| L/F | rs753245626 |
-1.892 | 0.942 | N | 0.746 | 0.314 | 0.305730143919 | gnomAD-4.0.0 | 2.12238E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.59921E-04 | 0 |
| L/S | rs1435172600 |
None | 0.942 | N | 0.703 | 0.503 | 0.826507983924 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/S | rs1435172600 |
None | 0.942 | N | 0.703 | 0.503 | 0.826507983924 | gnomAD-4.0.0 | 3.72061E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.0881E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8666 | likely_pathogenic | 0.7675 | pathogenic | -2.66 | Highly Destabilizing | 0.559 | D | 0.671 | neutral | None | None | None | None | N |
| L/C | 0.8436 | likely_pathogenic | 0.8162 | pathogenic | -2.059 | Highly Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| L/D | 0.9988 | likely_pathogenic | 0.9975 | pathogenic | -3.323 | Highly Destabilizing | 0.993 | D | 0.761 | deleterious | None | None | None | None | N |
| L/E | 0.9937 | likely_pathogenic | 0.9876 | pathogenic | -3.13 | Highly Destabilizing | 0.978 | D | 0.755 | deleterious | None | None | None | None | N |
| L/F | 0.7635 | likely_pathogenic | 0.7483 | pathogenic | -1.529 | Destabilizing | 0.942 | D | 0.746 | deleterious | N | 0.5106599 | None | None | N |
| L/G | 0.9801 | likely_pathogenic | 0.9622 | pathogenic | -3.164 | Highly Destabilizing | 0.978 | D | 0.75 | deleterious | None | None | None | None | N |
| L/H | 0.9927 | likely_pathogenic | 0.9882 | pathogenic | -2.656 | Highly Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| L/I | 0.2066 | likely_benign | 0.1621 | benign | -1.205 | Destabilizing | 0.247 | N | 0.721 | prob.delet. | N | 0.485089452 | None | None | N |
| L/K | 0.9928 | likely_pathogenic | 0.9871 | pathogenic | -2.21 | Highly Destabilizing | 0.978 | D | 0.684 | prob.neutral | None | None | None | None | N |
| L/M | 0.2541 | likely_benign | 0.2456 | benign | -1.228 | Destabilizing | 0.193 | N | 0.443 | neutral | None | None | None | None | N |
| L/N | 0.9907 | likely_pathogenic | 0.98 | pathogenic | -2.49 | Highly Destabilizing | 0.993 | D | 0.765 | deleterious | None | None | None | None | N |
| L/P | 0.9589 | likely_pathogenic | 0.9401 | pathogenic | -1.672 | Destabilizing | 0.993 | D | 0.759 | deleterious | None | None | None | None | N |
| L/Q | 0.9811 | likely_pathogenic | 0.9687 | pathogenic | -2.4 | Highly Destabilizing | 0.978 | D | 0.686 | prob.neutral | None | None | None | None | N |
| L/R | 0.9878 | likely_pathogenic | 0.9796 | pathogenic | -1.822 | Destabilizing | 0.978 | D | 0.695 | prob.neutral | None | None | None | None | N |
| L/S | 0.9862 | likely_pathogenic | 0.9703 | pathogenic | -3.087 | Highly Destabilizing | 0.942 | D | 0.703 | prob.neutral | N | 0.505972631 | None | None | N |
| L/T | 0.8626 | likely_pathogenic | 0.7428 | pathogenic | -2.769 | Highly Destabilizing | 0.86 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/V | 0.1438 | likely_benign | 0.114 | benign | -1.672 | Destabilizing | 0.006 | N | 0.328 | neutral | N | 0.461516372 | None | None | N |
| L/W | 0.968 | likely_pathogenic | 0.9608 | pathogenic | -1.978 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| L/Y | 0.9764 | likely_pathogenic | 0.972 | pathogenic | -1.739 | Destabilizing | 0.978 | D | 0.675 | neutral | 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.