Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4009 | 12250;12251;12252 | chr2:178741208;178741207;178741206 | chr2:179605935;179605934;179605933 |
| N2AB | 3692 | 11299;11300;11301 | chr2:178741208;178741207;178741206 | chr2:179605935;179605934;179605933 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3646 | 11161;11162;11163 | chr2:178741208;178741207;178741206 | chr2:179605935;179605934;179605933 |
| Novex-1 | 3771 | 11536;11537;11538 | chr2:178741208;178741207;178741206 | chr2:179605935;179605934;179605933 |
| Novex-2 | 3838 | 11737;11738;11739 | chr2:178741208;178741207;178741206 | chr2:179605935;179605934;179605933 |
| 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 | rs753367343  |
-0.867 | 1.0 | D | 0.868 | 0.79 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 8.9E-06 | 0 |
| Y/C | rs753367343 |
-0.867 | 1.0 | D | 0.868 | 0.79 | None | gnomAD-4.0.0 | 3.42219E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79887E-06 | 3.47802E-05 | 0 |
| Y/H | rs1166395538 |
-2.399 | 1.0 | D | 0.799 | 0.811 | None | 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 | rs1166395538 |
-2.399 | 1.0 | D | 0.799 | 0.811 | None | gnomAD-4.0.0 | 1.59249E-06 | None | None | None | None | N | None | 0 | 2.28686E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9896 | likely_pathogenic | 0.9907 | pathogenic | -1.396 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| Y/C | 0.8397 | likely_pathogenic | 0.8561 | pathogenic | -0.874 | Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.830460077 | None | None | N |
| Y/D | 0.991 | likely_pathogenic | 0.9937 | pathogenic | -2.388 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.830460076 | None | None | N |
| Y/E | 0.9961 | likely_pathogenic | 0.9971 | pathogenic | -2.184 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| Y/F | 0.1945 | likely_benign | 0.1894 | benign | -0.513 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | D | 0.650445156 | None | None | N |
| Y/G | 0.9824 | likely_pathogenic | 0.9844 | pathogenic | -1.758 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| Y/H | 0.9085 | likely_pathogenic | 0.9163 | pathogenic | -1.874 | Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.831105429 | None | None | N |
| Y/I | 0.8954 | likely_pathogenic | 0.9057 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| Y/K | 0.9955 | likely_pathogenic | 0.9969 | pathogenic | -1.439 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| Y/L | 0.7451 | likely_pathogenic | 0.7704 | pathogenic | -0.21 | Destabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | N |
| Y/M | 0.9654 | likely_pathogenic | 0.9655 | pathogenic | -0.407 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| Y/N | 0.955 | likely_pathogenic | 0.9636 | pathogenic | -2.294 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.830460076 | None | None | N |
| Y/P | 0.9924 | likely_pathogenic | 0.9937 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.912 | deleterious | None | None | None | None | N |
| Y/Q | 0.9943 | likely_pathogenic | 0.9951 | pathogenic | -1.778 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| Y/R | 0.9821 | likely_pathogenic | 0.9859 | pathogenic | -2.053 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| Y/S | 0.9695 | likely_pathogenic | 0.9737 | pathogenic | -2.349 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.830460076 | None | None | N |
| Y/T | 0.9896 | likely_pathogenic | 0.9903 | pathogenic | -2.014 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| Y/V | 0.8694 | likely_pathogenic | 0.8727 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| Y/W | 0.7571 | likely_pathogenic | 0.7389 | pathogenic | -0.177 | Destabilizing | 1.0 | D | 0.791 | 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.