Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25186 | 75781;75782;75783 | chr2:178570576;178570575;178570574 | chr2:179435303;179435302;179435301 |
| N2AB | 23545 | 70858;70859;70860 | chr2:178570576;178570575;178570574 | chr2:179435303;179435302;179435301 |
| N2A | 22618 | 68077;68078;68079 | chr2:178570576;178570575;178570574 | chr2:179435303;179435302;179435301 |
| N2B | 16121 | 48586;48587;48588 | chr2:178570576;178570575;178570574 | chr2:179435303;179435302;179435301 |
| Novex-1 | 16246 | 48961;48962;48963 | chr2:178570576;178570575;178570574 | chr2:179435303;179435302;179435301 |
| Novex-2 | 16313 | 49162;49163;49164 | chr2:178570576;178570575;178570574 | chr2:179435303;179435302;179435301 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs1305259914  |
-1.79 | 0.891 | D | 0.692 | 0.553 | 0.508455578974 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 1.66334E-04 |
| A/S | rs1305259914 |
-1.79 | 0.891 | D | 0.692 | 0.553 | 0.508455578974 | gnomAD-4.0.0 | 3.4219E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49792E-06 | 0 | 0 |
| A/T | None | None | 0.801 | D | 0.704 | 0.572 | 0.527709697666 | gnomAD-4.0.0 | 6.8438E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15939E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5622 | ambiguous | 0.5786 | pathogenic | -1.312 | Destabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | N |
| A/D | 0.9904 | likely_pathogenic | 0.9922 | pathogenic | -2.17 | Highly Destabilizing | 0.989 | D | 0.799 | deleterious | D | 0.615551992 | None | None | N |
| A/E | 0.9658 | likely_pathogenic | 0.9701 | pathogenic | -2.053 | Highly Destabilizing | 0.974 | D | 0.762 | deleterious | None | None | None | None | N |
| A/F | 0.86 | likely_pathogenic | 0.8677 | pathogenic | -0.9 | Destabilizing | 0.949 | D | 0.795 | deleterious | None | None | None | None | N |
| A/G | 0.3124 | likely_benign | 0.3376 | benign | -1.654 | Destabilizing | 0.891 | D | 0.707 | prob.neutral | D | 0.561518349 | None | None | N |
| A/H | 0.9905 | likely_pathogenic | 0.9916 | pathogenic | -1.942 | Destabilizing | 0.998 | D | 0.796 | deleterious | None | None | None | None | N |
| A/I | 0.322 | likely_benign | 0.3111 | benign | -0.193 | Destabilizing | 0.525 | D | 0.705 | prob.neutral | None | None | None | None | N |
| A/K | 0.9919 | likely_pathogenic | 0.9932 | pathogenic | -1.518 | Destabilizing | 0.974 | D | 0.763 | deleterious | None | None | None | None | N |
| A/L | 0.1817 | likely_benign | 0.1776 | benign | -0.193 | Destabilizing | 0.007 | N | 0.429 | neutral | None | None | None | None | N |
| A/M | 0.4084 | ambiguous | 0.4195 | ambiguous | -0.339 | Destabilizing | 0.949 | D | 0.761 | deleterious | None | None | None | None | N |
| A/N | 0.9657 | likely_pathogenic | 0.9704 | pathogenic | -1.565 | Destabilizing | 0.991 | D | 0.799 | deleterious | None | None | None | None | N |
| A/P | 0.9828 | likely_pathogenic | 0.9816 | pathogenic | -0.5 | Destabilizing | 0.989 | D | 0.777 | deleterious | D | 0.615350188 | None | None | N |
| A/Q | 0.9575 | likely_pathogenic | 0.9615 | pathogenic | -1.514 | Destabilizing | 0.991 | D | 0.765 | deleterious | None | None | None | None | N |
| A/R | 0.9833 | likely_pathogenic | 0.9852 | pathogenic | -1.39 | Destabilizing | 0.974 | D | 0.776 | deleterious | None | None | None | None | N |
| A/S | 0.3889 | ambiguous | 0.4147 | ambiguous | -1.982 | Destabilizing | 0.891 | D | 0.692 | prob.neutral | D | 0.57756807 | None | None | N |
| A/T | 0.278 | likely_benign | 0.2954 | benign | -1.754 | Destabilizing | 0.801 | D | 0.704 | prob.neutral | D | 0.582473888 | None | None | N |
| A/V | 0.1336 | likely_benign | 0.1339 | benign | -0.5 | Destabilizing | 0.005 | N | 0.277 | neutral | N | 0.493432081 | None | None | N |
| A/W | 0.9908 | likely_pathogenic | 0.9921 | pathogenic | -1.518 | Destabilizing | 0.998 | D | 0.824 | deleterious | None | None | None | None | N |
| A/Y | 0.9632 | likely_pathogenic | 0.9679 | pathogenic | -1.041 | Destabilizing | 0.974 | D | 0.799 | 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.