Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27189 | 81790;81791;81792 | chr2:178564567;178564566;178564565 | chr2:179429294;179429293;179429292 |
| N2AB | 25548 | 76867;76868;76869 | chr2:178564567;178564566;178564565 | chr2:179429294;179429293;179429292 |
| N2A | 24621 | 74086;74087;74088 | chr2:178564567;178564566;178564565 | chr2:179429294;179429293;179429292 |
| N2B | 18124 | 54595;54596;54597 | chr2:178564567;178564566;178564565 | chr2:179429294;179429293;179429292 |
| Novex-1 | 18249 | 54970;54971;54972 | chr2:178564567;178564566;178564565 | chr2:179429294;179429293;179429292 |
| Novex-2 | 18316 | 55171;55172;55173 | chr2:178564567;178564566;178564565 | chr2:179429294;179429293;179429292 |
| 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/V | rs142391957  |
-1.247 | 0.999 | N | 0.546 | 0.335 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 2.89495E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs142391957 |
-1.247 | 0.999 | N | 0.546 | 0.335 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 2.89673E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs142391957 |
-1.247 | 0.999 | N | 0.546 | 0.335 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/V | rs142391957 |
-1.247 | 0.999 | N | 0.546 | 0.335 | None | gnomAD-4.0.0 | 1.54951E-05 | None | None | None | None | N | None | 2.93318E-04 | 1.66744E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20184E-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 | 0.9615 | likely_pathogenic | 0.9567 | pathogenic | -2.852 | Highly Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| L/C | 0.9286 | likely_pathogenic | 0.9226 | pathogenic | -1.62 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -3.306 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| L/E | 0.9973 | likely_pathogenic | 0.997 | pathogenic | -2.977 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| L/F | 0.7889 | likely_pathogenic | 0.7433 | pathogenic | -1.618 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| L/G | 0.9959 | likely_pathogenic | 0.9954 | pathogenic | -3.444 | Highly Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/H | 0.9964 | likely_pathogenic | 0.9955 | pathogenic | -3.108 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/I | 0.0901 | likely_benign | 0.0833 | benign | -1.048 | Destabilizing | 0.999 | D | 0.52 | neutral | None | None | None | None | N |
| L/K | 0.9963 | likely_pathogenic | 0.9957 | pathogenic | -1.953 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| L/M | 0.3528 | ambiguous | 0.3245 | benign | -1.201 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.536042302 | None | None | N |
| L/N | 0.9981 | likely_pathogenic | 0.9978 | pathogenic | -2.689 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| L/P | 0.9975 | likely_pathogenic | 0.9972 | pathogenic | -1.644 | Destabilizing | 1.0 | D | 0.906 | deleterious | D | 0.568896677 | None | None | N |
| L/Q | 0.9923 | likely_pathogenic | 0.9906 | pathogenic | -2.292 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.568896677 | None | None | N |
| L/R | 0.993 | likely_pathogenic | 0.9922 | pathogenic | -2.115 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.568896677 | None | None | N |
| L/S | 0.9958 | likely_pathogenic | 0.9946 | pathogenic | -3.155 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/T | 0.9692 | likely_pathogenic | 0.9637 | pathogenic | -2.668 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| L/V | 0.1176 | likely_benign | 0.1102 | benign | -1.644 | Destabilizing | 0.999 | D | 0.546 | neutral | N | 0.485010177 | None | None | N |
| L/W | 0.9862 | likely_pathogenic | 0.9834 | pathogenic | -1.921 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| L/Y | 0.9878 | likely_pathogenic | 0.9857 | pathogenic | -1.813 | Destabilizing | 1.0 | D | 0.778 | 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.