Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22817 | 68674;68675;68676 | chr2:178578066;178578065;178578064 | chr2:179442793;179442792;179442791 |
| N2AB | 21176 | 63751;63752;63753 | chr2:178578066;178578065;178578064 | chr2:179442793;179442792;179442791 |
| N2A | 20249 | 60970;60971;60972 | chr2:178578066;178578065;178578064 | chr2:179442793;179442792;179442791 |
| N2B | 13752 | 41479;41480;41481 | chr2:178578066;178578065;178578064 | chr2:179442793;179442792;179442791 |
| Novex-1 | 13877 | 41854;41855;41856 | chr2:178578066;178578065;178578064 | chr2:179442793;179442792;179442791 |
| Novex-2 | 13944 | 42055;42056;42057 | chr2:178578066;178578065;178578064 | chr2:179442793;179442792;179442791 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs372496072  |
-1.042 | 1.0 | N | 0.735 | 0.446 | 0.425970041486 | gnomAD-2.1.1 | 4.29E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 4.64588E-04 | None | 3.27E-05 | None | 0 | 7.84E-06 | 0 |
| R/Q | rs372496072 |
-1.042 | 1.0 | N | 0.735 | 0.446 | 0.425970041486 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 7.74593E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs372496072 |
-1.042 | 1.0 | N | 0.735 | 0.446 | 0.425970041486 | gnomAD-4.0.0 | 1.36374E-05 | None | None | None | None | N | None | 1.33376E-05 | 1.667E-05 | None | 0 | 2.90555E-04 | None | 0 | 0 | 1.69569E-06 | 4.3929E-05 | 1.60113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9873 | likely_pathogenic | 0.9883 | pathogenic | -1.85 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| R/C | 0.7203 | likely_pathogenic | 0.7442 | pathogenic | -1.754 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/D | 0.999 | likely_pathogenic | 0.999 | pathogenic | -1.152 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| R/E | 0.985 | likely_pathogenic | 0.9833 | pathogenic | -0.93 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| R/F | 0.9939 | likely_pathogenic | 0.9947 | pathogenic | -0.908 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| R/G | 0.9854 | likely_pathogenic | 0.9876 | pathogenic | -2.179 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | D | 0.556782087 | None | None | N |
| R/H | 0.6405 | likely_pathogenic | 0.6313 | pathogenic | -2.04 | Highly Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/I | 0.9727 | likely_pathogenic | 0.9782 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| R/K | 0.5184 | ambiguous | 0.5552 | ambiguous | -1.183 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| R/L | 0.9496 | likely_pathogenic | 0.9556 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | D | 0.527575016 | None | None | N |
| R/M | 0.9751 | likely_pathogenic | 0.9785 | pathogenic | -1.452 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/N | 0.9956 | likely_pathogenic | 0.9959 | pathogenic | -1.377 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.557289066 | None | None | N |
| R/Q | 0.6238 | likely_pathogenic | 0.6019 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.487439259 | None | None | N |
| R/S | 0.9911 | likely_pathogenic | 0.992 | pathogenic | -2.097 | Highly Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/T | 0.9871 | likely_pathogenic | 0.9895 | pathogenic | -1.674 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/V | 0.9753 | likely_pathogenic | 0.9779 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/W | 0.9165 | likely_pathogenic | 0.9269 | pathogenic | -0.575 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/Y | 0.9776 | likely_pathogenic | 0.9804 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.821 | 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.