Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23430 | 70513;70514;70515 | chr2:178575844;178575843;178575842 | chr2:179440571;179440570;179440569 |
| N2AB | 21789 | 65590;65591;65592 | chr2:178575844;178575843;178575842 | chr2:179440571;179440570;179440569 |
| N2A | 20862 | 62809;62810;62811 | chr2:178575844;178575843;178575842 | chr2:179440571;179440570;179440569 |
| N2B | 14365 | 43318;43319;43320 | chr2:178575844;178575843;178575842 | chr2:179440571;179440570;179440569 |
| Novex-1 | 14490 | 43693;43694;43695 | chr2:178575844;178575843;178575842 | chr2:179440571;179440570;179440569 |
| Novex-2 | 14557 | 43894;43895;43896 | chr2:178575844;178575843;178575842 | chr2:179440571;179440570;179440569 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs549709481  |
-1.647 | 1.0 | N | 0.828 | 0.433 | 0.814958828484 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| V/F | rs549709481 |
-1.647 | 1.0 | N | 0.828 | 0.433 | 0.814958828484 | gnomAD-4.0.0 | 2.73721E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59834E-06 | 0 | 0 |
| V/I | rs549709481 |
-0.579 | 0.999 | N | 0.537 | 0.224 | 0.508994031223 | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 2.6154E-04 | None | 0 | 0 | 1.4041E-04 |
| V/I | rs549709481 |
-0.579 | 0.999 | N | 0.537 | 0.224 | 0.508994031223 | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 6.22407E-04 | 0 |
| V/I | rs549709481 |
-0.579 | 0.999 | N | 0.537 | 0.224 | 0.508994031223 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/I | rs549709481 |
-0.579 | 0.999 | N | 0.537 | 0.224 | 0.508994031223 | gnomAD-4.0.0 | 4.71014E-05 | None | None | None | None | N | None | 5.33305E-05 | 0 | None | 0 | 0 | None | 1.5623E-05 | 0 | 2.96706E-05 | 3.73388E-04 | 3.20143E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9421 | likely_pathogenic | 0.9541 | pathogenic | -2.318 | Highly Destabilizing | 0.999 | D | 0.607 | neutral | N | 0.508962284 | None | None | N |
| V/C | 0.9659 | likely_pathogenic | 0.9701 | pathogenic | -2.047 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| V/D | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -2.771 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | N | 0.509469263 | None | None | N |
| V/E | 0.9979 | likely_pathogenic | 0.9978 | pathogenic | -2.577 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/F | 0.9445 | likely_pathogenic | 0.9502 | pathogenic | -1.457 | Destabilizing | 1.0 | D | 0.828 | deleterious | N | 0.508201816 | None | None | N |
| V/G | 0.9736 | likely_pathogenic | 0.9757 | pathogenic | -2.856 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | N | 0.509469263 | None | None | N |
| V/H | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -2.499 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| V/I | 0.1417 | likely_benign | 0.1524 | benign | -0.824 | Destabilizing | 0.999 | D | 0.537 | neutral | N | 0.511333825 | None | None | N |
| V/K | 0.998 | likely_pathogenic | 0.9979 | pathogenic | -2.043 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/L | 0.7987 | likely_pathogenic | 0.8338 | pathogenic | -0.824 | Destabilizing | 0.999 | D | 0.629 | neutral | N | 0.432272627 | None | None | N |
| V/M | 0.8769 | likely_pathogenic | 0.8924 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| V/N | 0.9975 | likely_pathogenic | 0.9975 | pathogenic | -2.301 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| V/P | 0.9976 | likely_pathogenic | 0.998 | pathogenic | -1.294 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| V/Q | 0.9974 | likely_pathogenic | 0.9972 | pathogenic | -2.188 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/R | 0.9958 | likely_pathogenic | 0.9957 | pathogenic | -1.763 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| V/S | 0.9897 | likely_pathogenic | 0.9911 | pathogenic | -2.975 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/T | 0.9431 | likely_pathogenic | 0.954 | pathogenic | -2.632 | Highly Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| V/W | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -1.91 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| V/Y | 0.9965 | likely_pathogenic | 0.9966 | pathogenic | -1.58 | Destabilizing | 1.0 | D | 0.827 | 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.