Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19857 | 59794;59795;59796 | chr2:178592436;178592435;178592434 | chr2:179457163;179457162;179457161 |
| N2AB | 18216 | 54871;54872;54873 | chr2:178592436;178592435;178592434 | chr2:179457163;179457162;179457161 |
| N2A | 17289 | 52090;52091;52092 | chr2:178592436;178592435;178592434 | chr2:179457163;179457162;179457161 |
| N2B | 10792 | 32599;32600;32601 | chr2:178592436;178592435;178592434 | chr2:179457163;179457162;179457161 |
| Novex-1 | 10917 | 32974;32975;32976 | chr2:178592436;178592435;178592434 | chr2:179457163;179457162;179457161 |
| Novex-2 | 10984 | 33175;33176;33177 | chr2:178592436;178592435;178592434 | chr2:179457163;179457162;179457161 |
| 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/S | rs547180437  |
-2.984 | 1.0 | N | 0.917 | 0.551 | 0.758188736314 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93798E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/S | rs547180437 |
-2.984 | 1.0 | N | 0.917 | 0.551 | 0.758188736314 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| L/S | rs547180437 |
-2.984 | 1.0 | N | 0.917 | 0.551 | 0.758188736314 | gnomAD-4.0.0 | 1.54942E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.46608E-05 | None | 0 | 0 | 1.86503E-05 | 0 | 1.60077E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9582 | likely_pathogenic | 0.9627 | pathogenic | -2.434 | Highly Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | N |
| L/C | 0.907 | likely_pathogenic | 0.909 | pathogenic | -2.058 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -2.451 | Highly Destabilizing | 1.0 | D | 0.935 | deleterious | None | None | None | None | N |
| L/E | 0.9976 | likely_pathogenic | 0.9981 | pathogenic | -2.3 | Highly Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| L/F | 0.7809 | likely_pathogenic | 0.7329 | pathogenic | -1.675 | Destabilizing | 1.0 | D | 0.855 | deleterious | N | 0.468872072 | None | None | N |
| L/G | 0.9955 | likely_pathogenic | 0.9964 | pathogenic | -2.921 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/H | 0.9949 | likely_pathogenic | 0.9957 | pathogenic | -2.284 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/I | 0.1562 | likely_benign | 0.1266 | benign | -1.064 | Destabilizing | 0.999 | D | 0.674 | neutral | N | 0.444548685 | None | None | N |
| L/K | 0.9945 | likely_pathogenic | 0.9957 | pathogenic | -1.76 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| L/M | 0.3318 | likely_benign | 0.3193 | benign | -1.065 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| L/N | 0.9977 | likely_pathogenic | 0.9981 | pathogenic | -1.942 | Destabilizing | 1.0 | D | 0.936 | deleterious | None | None | None | None | N |
| L/P | 0.9978 | likely_pathogenic | 0.9985 | pathogenic | -1.498 | Destabilizing | 1.0 | D | 0.936 | deleterious | None | None | None | None | N |
| L/Q | 0.9897 | likely_pathogenic | 0.9919 | pathogenic | -1.936 | Destabilizing | 1.0 | D | 0.939 | deleterious | None | None | None | None | N |
| L/R | 0.9898 | likely_pathogenic | 0.9924 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | None | N |
| L/S | 0.9965 | likely_pathogenic | 0.9968 | pathogenic | -2.694 | Highly Destabilizing | 1.0 | D | 0.917 | deleterious | N | 0.488497264 | None | None | N |
| L/T | 0.9837 | likely_pathogenic | 0.9844 | pathogenic | -2.396 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/V | 0.2285 | likely_benign | 0.1987 | benign | -1.498 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | N | 0.450589223 | None | None | N |
| L/W | 0.9844 | likely_pathogenic | 0.9871 | pathogenic | -1.928 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| L/Y | 0.9851 | likely_pathogenic | 0.9852 | pathogenic | -1.66 | Destabilizing | 1.0 | D | 0.897 | 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.