Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23527 | 70804;70805;70806 | chr2:178575553;178575552;178575551 | chr2:179440280;179440279;179440278 |
| N2AB | 21886 | 65881;65882;65883 | chr2:178575553;178575552;178575551 | chr2:179440280;179440279;179440278 |
| N2A | 20959 | 63100;63101;63102 | chr2:178575553;178575552;178575551 | chr2:179440280;179440279;179440278 |
| N2B | 14462 | 43609;43610;43611 | chr2:178575553;178575552;178575551 | chr2:179440280;179440279;179440278 |
| Novex-1 | 14587 | 43984;43985;43986 | chr2:178575553;178575552;178575551 | chr2:179440280;179440279;179440278 |
| Novex-2 | 14654 | 44185;44186;44187 | chr2:178575553;178575552;178575551 | chr2:179440280;179440279;179440278 |
| 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/I | rs542004766  |
-0.358 | None | N | 0.123 | 0.047 | None | gnomAD-2.1.1 | 4.64E-05 | None | None | None | None | N | None | 1.65358E-04 | 5.65E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 4.7E-05 | 0 |
| V/I | rs542004766 |
-0.358 | None | N | 0.123 | 0.047 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 9.65E-05 | 1.31044E-04 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/I | rs542004766 |
-0.358 | None | N | 0.123 | 0.047 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs542004766 |
-0.358 | None | N | 0.123 | 0.047 | None | gnomAD-4.0.0 | 2.60283E-05 | None | None | None | None | N | None | 9.3301E-05 | 6.66622E-05 | None | 0 | 0 | None | 0 | 0 | 1.86498E-05 | 5.49028E-05 | 6.40266E-05 |
| V/L | rs542004766 |
-0.361 | None | N | 0.219 | 0.053 | 0.317378411342 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| V/L | rs542004766 |
-0.361 | None | N | 0.219 | 0.053 | 0.317378411342 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs542004766 |
-0.361 | None | N | 0.219 | 0.053 | 0.317378411342 | gnomAD-4.0.0 | 2.47907E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39084E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.5056 | ambiguous | 0.4913 | ambiguous | -1.903 | Destabilizing | 0.256 | N | 0.574 | neutral | N | 0.491226877 | None | None | N |
| V/C | 0.7661 | likely_pathogenic | 0.775 | pathogenic | -1.196 | Destabilizing | 0.989 | D | 0.612 | neutral | None | None | None | None | N |
| V/D | 0.9479 | likely_pathogenic | 0.9581 | pathogenic | -2.297 | Highly Destabilizing | 0.983 | D | 0.797 | deleterious | None | None | None | None | N |
| V/E | 0.8127 | likely_pathogenic | 0.8317 | pathogenic | -2.099 | Highly Destabilizing | 0.878 | D | 0.685 | prob.delet. | N | 0.510091601 | None | None | N |
| V/F | 0.3033 | likely_benign | 0.3142 | benign | -1.174 | Destabilizing | 0.878 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/G | 0.7085 | likely_pathogenic | 0.7122 | pathogenic | -2.391 | Highly Destabilizing | 0.952 | D | 0.777 | deleterious | N | 0.51059858 | None | None | N |
| V/H | 0.8921 | likely_pathogenic | 0.8967 | pathogenic | -1.934 | Destabilizing | 0.992 | D | 0.726 | deleterious | None | None | None | None | N |
| V/I | 0.0711 | likely_benign | 0.0705 | benign | -0.555 | Destabilizing | None | N | 0.123 | neutral | N | 0.449693507 | None | None | N |
| V/K | 0.8364 | likely_pathogenic | 0.8477 | pathogenic | -1.607 | Destabilizing | 0.872 | D | 0.689 | prob.delet. | None | None | None | None | N |
| V/L | 0.2428 | likely_benign | 0.2226 | benign | -0.555 | Destabilizing | None | N | 0.219 | neutral | N | 0.501871767 | None | None | N |
| V/M | 0.2018 | likely_benign | 0.1903 | benign | -0.45 | Destabilizing | 0.837 | D | 0.68 | prob.neutral | None | None | None | None | N |
| V/N | 0.8501 | likely_pathogenic | 0.8613 | pathogenic | -1.853 | Destabilizing | 0.755 | D | 0.79 | deleterious | None | None | None | None | N |
| V/P | 0.9809 | likely_pathogenic | 0.9853 | pathogenic | -0.977 | Destabilizing | 0.755 | D | 0.707 | prob.delet. | None | None | None | None | N |
| V/Q | 0.7354 | likely_pathogenic | 0.7312 | pathogenic | -1.752 | Destabilizing | 0.936 | D | 0.659 | prob.neutral | None | None | None | None | N |
| V/R | 0.784 | likely_pathogenic | 0.8021 | pathogenic | -1.372 | Destabilizing | 0.978 | D | 0.793 | deleterious | None | None | None | None | N |
| V/S | 0.6844 | likely_pathogenic | 0.6823 | pathogenic | -2.441 | Highly Destabilizing | 0.691 | D | 0.671 | prob.neutral | None | None | None | None | N |
| V/T | 0.4643 | ambiguous | 0.4325 | ambiguous | -2.102 | Highly Destabilizing | 0.308 | N | 0.604 | neutral | None | None | None | None | N |
| V/W | 0.9184 | likely_pathogenic | 0.9273 | pathogenic | -1.602 | Destabilizing | 0.998 | D | 0.755 | deleterious | None | None | None | None | N |
| V/Y | 0.7645 | likely_pathogenic | 0.7962 | pathogenic | -1.202 | Destabilizing | 0.936 | D | 0.727 | 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.