Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16228 | 48907;48908;48909 | chr2:178614925;178614924;178614923 | chr2:179479652;179479651;179479650 |
| N2AB | 14587 | 43984;43985;43986 | chr2:178614925;178614924;178614923 | chr2:179479652;179479651;179479650 |
| N2A | 13660 | 41203;41204;41205 | chr2:178614925;178614924;178614923 | chr2:179479652;179479651;179479650 |
| N2B | 7163 | 21712;21713;21714 | chr2:178614925;178614924;178614923 | chr2:179479652;179479651;179479650 |
| Novex-1 | 7288 | 22087;22088;22089 | chr2:178614925;178614924;178614923 | chr2:179479652;179479651;179479650 |
| Novex-2 | 7355 | 22288;22289;22290 | chr2:178614925;178614924;178614923 | chr2:179479652;179479651;179479650 |
| 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/C | rs371305932  |
-1.388 | 1.0 | D | 0.805 | 0.502 | None | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 4.46E-05 | 0 | None | 0 | 1.72851E-04 | None | 0 | None | 0 | 3.55E-05 | 0 |
| R/C | rs371305932 |
-1.388 | 1.0 | D | 0.805 | 0.502 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/C | rs371305932 |
-1.388 | 1.0 | D | 0.805 | 0.502 | None | gnomAD-4.0.0 | 3.26363E-05 | None | None | None | None | N | None | 1.34153E-05 | 0 | None | 0 | 4.54959E-05 | None | 0 | 0 | 3.67857E-05 | 3.41087E-05 | 4.86113E-05 |
| R/H | rs368806005 |
-1.923 | 1.0 | D | 0.821 | 0.529 | None | gnomAD-2.1.1 | 1.71151E-04 | None | None | None | None | N | None | 0 | 3.43235E-04 | None | 0 | 0 | None | 7.39E-05 | None | 2.13183E-04 | 2.13242E-04 | 1.51423E-04 |
| R/H | rs368806005 |
-1.923 | 1.0 | D | 0.821 | 0.529 | None | gnomAD-3.1.2 | 1.11945E-04 | None | None | None | None | N | None | 4.83E-05 | 2.62536E-04 | 0 | 0 | 0 | None | 3.76932E-04 | 0 | 1.03081E-04 | 0 | 0 |
| R/H | rs368806005 |
-1.923 | 1.0 | D | 0.821 | 0.529 | None | gnomAD-4.0.0 | 8.59924E-05 | None | None | None | None | N | None | 5.36337E-05 | 2.44909E-04 | None | 0 | 4.54794E-05 | None | 2.22639E-04 | 0 | 7.44381E-05 | 6.82423E-05 | 1.62048E-04 |
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 | 0.9902 | likely_pathogenic | 0.9772 | pathogenic | -1.799 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| R/C | 0.8439 | likely_pathogenic | 0.8028 | pathogenic | -1.726 | Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.732917411 | None | None | N |
| R/D | 0.9992 | likely_pathogenic | 0.9984 | pathogenic | -1.004 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/E | 0.9869 | likely_pathogenic | 0.9693 | pathogenic | -0.79 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/F | 0.997 | likely_pathogenic | 0.9927 | pathogenic | -0.964 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| R/G | 0.986 | likely_pathogenic | 0.9724 | pathogenic | -2.128 | Highly Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.766120958 | None | None | N |
| R/H | 0.8083 | likely_pathogenic | 0.6766 | pathogenic | -2.048 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | D | 0.72148313 | None | None | N |
| R/I | 0.9871 | likely_pathogenic | 0.9662 | pathogenic | -0.843 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| R/K | 0.7959 | likely_pathogenic | 0.5977 | pathogenic | -1.163 | Destabilizing | 0.998 | D | 0.668 | neutral | None | None | None | None | N |
| R/L | 0.978 | likely_pathogenic | 0.9438 | pathogenic | -0.843 | Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.696204113 | None | None | N |
| R/M | 0.9898 | likely_pathogenic | 0.9644 | pathogenic | -1.399 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/N | 0.9968 | likely_pathogenic | 0.9937 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/P | 0.9996 | likely_pathogenic | 0.9993 | pathogenic | -1.151 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.799574882 | None | None | N |
| R/Q | 0.6983 | likely_pathogenic | 0.4858 | ambiguous | -1.002 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| R/S | 0.995 | likely_pathogenic | 0.9889 | pathogenic | -1.999 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.647844941 | None | None | N |
| R/T | 0.9908 | likely_pathogenic | 0.9733 | pathogenic | -1.582 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| R/V | 0.9851 | likely_pathogenic | 0.9637 | pathogenic | -1.151 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| R/W | 0.9645 | likely_pathogenic | 0.9168 | pathogenic | -0.606 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| R/Y | 0.9903 | likely_pathogenic | 0.9789 | pathogenic | -0.437 | Destabilizing | 1.0 | D | 0.833 | 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.