Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19583 | 58972;58973;58974 | chr2:178593461;178593460;178593459 | chr2:179458188;179458187;179458186 |
| N2AB | 17942 | 54049;54050;54051 | chr2:178593461;178593460;178593459 | chr2:179458188;179458187;179458186 |
| N2A | 17015 | 51268;51269;51270 | chr2:178593461;178593460;178593459 | chr2:179458188;179458187;179458186 |
| N2B | 10518 | 31777;31778;31779 | chr2:178593461;178593460;178593459 | chr2:179458188;179458187;179458186 |
| Novex-1 | 10643 | 32152;32153;32154 | chr2:178593461;178593460;178593459 | chr2:179458188;179458187;179458186 |
| Novex-2 | 10710 | 32353;32354;32355 | chr2:178593461;178593460;178593459 | chr2:179458188;179458187;179458186 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs758600822  |
-2.131 | 1.0 | D | 0.794 | 0.596 | 0.706349033832 | gnomAD-2.1.1 | 1.8E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.92E-05 | 0 |
| P/A | rs758600822 |
-2.131 | 1.0 | D | 0.794 | 0.596 | 0.706349033832 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| P/A | rs758600822 |
-2.131 | 1.0 | D | 0.794 | 0.596 | 0.706349033832 | gnomAD-4.0.0 | 2.17282E-05 | None | None | None | None | N | None | 4.01735E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62878E-05 | 0 | 1.60406E-05 |
| P/L | rs1206288937 |
-0.484 | 1.0 | D | 0.889 | 0.618 | 0.758979986344 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.66E-05 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs1206288937 |
-0.484 | 1.0 | D | 0.889 | 0.618 | 0.758979986344 | gnomAD-4.0.0 | 1.59847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78816E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs1206288937 |
-1.59 | 1.0 | D | 0.921 | 0.62 | 0.810174296794 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| P/R | rs1206288937 |
-1.59 | 1.0 | D | 0.921 | 0.62 | 0.810174296794 | 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 |
| P/R | rs1206288937 |
-1.59 | 1.0 | D | 0.921 | 0.62 | 0.810174296794 | gnomAD-4.0.0 | 2.57196E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79246E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6993 | likely_pathogenic | 0.6258 | pathogenic | -1.944 | Destabilizing | 1.0 | D | 0.794 | deleterious | D | 0.603245471 | None | None | N |
| P/C | 0.909 | likely_pathogenic | 0.8746 | pathogenic | -2.156 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| P/D | 0.9989 | likely_pathogenic | 0.9986 | pathogenic | -3.399 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| P/E | 0.9973 | likely_pathogenic | 0.9965 | pathogenic | -3.265 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| P/F | 0.9985 | likely_pathogenic | 0.9979 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| P/G | 0.9822 | likely_pathogenic | 0.978 | pathogenic | -2.368 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| P/H | 0.9965 | likely_pathogenic | 0.9945 | pathogenic | -1.941 | Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.657480918 | None | None | N |
| P/I | 0.9631 | likely_pathogenic | 0.9539 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | None | N |
| P/K | 0.9981 | likely_pathogenic | 0.9973 | pathogenic | -1.756 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| P/L | 0.9046 | likely_pathogenic | 0.8743 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.889 | deleterious | D | 0.640825784 | None | None | N |
| P/M | 0.9772 | likely_pathogenic | 0.9713 | pathogenic | -1.106 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| P/N | 0.9982 | likely_pathogenic | 0.9977 | pathogenic | -2.103 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| P/Q | 0.9936 | likely_pathogenic | 0.9906 | pathogenic | -2.101 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| P/R | 0.9934 | likely_pathogenic | 0.9902 | pathogenic | -1.427 | Destabilizing | 1.0 | D | 0.921 | deleterious | D | 0.657279114 | None | None | N |
| P/S | 0.965 | likely_pathogenic | 0.9486 | pathogenic | -2.526 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | D | 0.631539198 | None | None | N |
| P/T | 0.9292 | likely_pathogenic | 0.8998 | pathogenic | -2.276 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | D | 0.619900605 | None | None | N |
| P/V | 0.874 | likely_pathogenic | 0.8521 | pathogenic | -1.148 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| P/W | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -1.58 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| P/Y | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -1.282 | Destabilizing | 1.0 | D | 0.92 | 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.