Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31545 | 94858;94859;94860 | chr2:178546795;178546794;178546793 | chr2:179411522;179411521;179411520 |
| N2AB | 29904 | 89935;89936;89937 | chr2:178546795;178546794;178546793 | chr2:179411522;179411521;179411520 |
| N2A | 28977 | 87154;87155;87156 | chr2:178546795;178546794;178546793 | chr2:179411522;179411521;179411520 |
| N2B | 22480 | 67663;67664;67665 | chr2:178546795;178546794;178546793 | chr2:179411522;179411521;179411520 |
| Novex-1 | 22605 | 68038;68039;68040 | chr2:178546795;178546794;178546793 | chr2:179411522;179411521;179411520 |
| Novex-2 | 22672 | 68239;68240;68241 | chr2:178546795;178546794;178546793 | chr2:179411522;179411521;179411520 |
| 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 | rs202187398  |
-2.03 | 1.0 | N | 0.775 | 0.422 | None | gnomAD-2.1.1 | 2.04067E-04 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 6.8049E-04 | 2.90474E-04 | 2.81452E-04 |
| R/C | rs202187398 |
-2.03 | 1.0 | N | 0.775 | 0.422 | None | gnomAD-3.1.2 | 2.23543E-04 | None | None | None | None | N | None | 0 | 1.31113E-04 | 0 | 0 | 0 | None | 2.82965E-04 | 0 | 4.26395E-04 | 0 | 0 |
| R/C | rs202187398 |
-2.03 | 1.0 | N | 0.775 | 0.422 | None | gnomAD-4.0.0 | 1.3263E-04 | None | None | None | None | N | None | 0 | 5.00283E-05 | None | 0 | 0 | None | 4.84451E-04 | 0 | 1.46649E-04 | 0 | 1.12079E-04 |
| R/H | rs920039018 |
-2.298 | 1.0 | N | 0.721 | 0.388 | 0.336892272479 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 4.65E-05 | 0 | 0 |
| R/H | rs920039018 |
-2.298 | 1.0 | N | 0.721 | 0.388 | 0.336892272479 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs920039018 |
-2.298 | 1.0 | N | 0.721 | 0.388 | 0.336892272479 | gnomAD-4.0.0 | 1.61134E-05 | None | None | None | None | N | None | 1.33526E-05 | 0 | None | 3.37906E-05 | 2.22926E-05 | None | 1.56245E-05 | 0 | 1.69531E-05 | 2.19611E-05 | 0 |
| R/S | rs202187398 |
-2.8 | 0.996 | N | 0.705 | 0.384 | 0.341696514166 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/S | rs202187398 |
-2.8 | 0.996 | N | 0.705 | 0.384 | 0.341696514166 | gnomAD-4.0.0 | 6.84269E-07 | None | None | None | None | N | None | 2.98882E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.974 | likely_pathogenic | 0.9435 | pathogenic | -2.125 | Highly Destabilizing | 0.992 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/C | 0.6318 | likely_pathogenic | 0.4557 | ambiguous | -2.151 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.489887432 | None | None | N |
| R/D | 0.9961 | likely_pathogenic | 0.9918 | pathogenic | -1.662 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| R/E | 0.9488 | likely_pathogenic | 0.9034 | pathogenic | -1.406 | Destabilizing | 0.992 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/F | 0.9783 | likely_pathogenic | 0.9528 | pathogenic | -1.206 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| R/G | 0.9434 | likely_pathogenic | 0.8919 | pathogenic | -2.5 | Highly Destabilizing | 0.998 | D | 0.739 | prob.delet. | N | 0.500411271 | None | None | N |
| R/H | 0.5515 | ambiguous | 0.4048 | ambiguous | -1.777 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.482053527 | None | None | N |
| R/I | 0.9562 | likely_pathogenic | 0.8943 | pathogenic | -1.015 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/K | 0.2827 | likely_benign | 0.1979 | benign | -1.3 | Destabilizing | 0.611 | D | 0.39 | neutral | None | None | None | None | N |
| R/L | 0.9119 | likely_pathogenic | 0.8203 | pathogenic | -1.015 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | N | 0.476872059 | None | None | N |
| R/M | 0.9169 | likely_pathogenic | 0.8133 | pathogenic | -1.473 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/N | 0.9886 | likely_pathogenic | 0.9737 | pathogenic | -1.992 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/P | 0.9991 | likely_pathogenic | 0.998 | pathogenic | -1.377 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.515641917 | None | None | N |
| R/Q | 0.4295 | ambiguous | 0.2959 | benign | -1.765 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/S | 0.9843 | likely_pathogenic | 0.9626 | pathogenic | -2.795 | Highly Destabilizing | 0.996 | D | 0.705 | prob.neutral | N | 0.477027097 | None | None | N |
| R/T | 0.9744 | likely_pathogenic | 0.9291 | pathogenic | -2.3 | Highly Destabilizing | 0.999 | D | 0.71 | prob.delet. | None | None | None | None | N |
| R/V | 0.9582 | likely_pathogenic | 0.9029 | pathogenic | -1.377 | Destabilizing | 0.999 | D | 0.792 | deleterious | None | None | None | None | N |
| R/W | 0.7869 | likely_pathogenic | 0.6721 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/Y | 0.8742 | likely_pathogenic | 0.7924 | pathogenic | -0.645 | Destabilizing | 1.0 | D | 0.795 | 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.