Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22373 | 67342;67343;67344 | chr2:178580170;178580169;178580168 | chr2:179444897;179444896;179444895 |
| N2AB | 20732 | 62419;62420;62421 | chr2:178580170;178580169;178580168 | chr2:179444897;179444896;179444895 |
| N2A | 19805 | 59638;59639;59640 | chr2:178580170;178580169;178580168 | chr2:179444897;179444896;179444895 |
| N2B | 13308 | 40147;40148;40149 | chr2:178580170;178580169;178580168 | chr2:179444897;179444896;179444895 |
| Novex-1 | 13433 | 40522;40523;40524 | chr2:178580170;178580169;178580168 | chr2:179444897;179444896;179444895 |
| Novex-2 | 13500 | 40723;40724;40725 | chr2:178580170;178580169;178580168 | chr2:179444897;179444896;179444895 |
| 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/A | rs774568339  |
-1.951 | 0.052 | N | 0.515 | 0.352 | 0.505701759113 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/D | rs774568339 |
None | 0.484 | N | 0.793 | 0.605 | 0.789505694734 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/D | rs774568339 |
None | 0.484 | N | 0.793 | 0.605 | 0.789505694734 | gnomAD-4.0.0 | 3.71943E-06 | None | None | None | None | N | None | 5.34074E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47813E-07 | 0 | 1.602E-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 | 0.8194 | likely_pathogenic | 0.7798 | pathogenic | -1.707 | Destabilizing | 0.052 | N | 0.515 | neutral | N | 0.483160071 | None | None | N |
| V/C | 0.9036 | likely_pathogenic | 0.8789 | pathogenic | -0.712 | Destabilizing | 0.935 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/D | 0.9957 | likely_pathogenic | 0.995 | pathogenic | -2.574 | Highly Destabilizing | 0.484 | N | 0.793 | deleterious | N | 0.5021137 | None | None | N |
| V/E | 0.9871 | likely_pathogenic | 0.9856 | pathogenic | -2.239 | Highly Destabilizing | 0.555 | D | 0.746 | deleterious | None | None | None | None | N |
| V/F | 0.5233 | ambiguous | 0.4414 | ambiguous | -0.951 | Destabilizing | None | N | 0.554 | neutral | N | 0.482906582 | None | None | N |
| V/G | 0.9234 | likely_pathogenic | 0.9108 | pathogenic | -2.315 | Highly Destabilizing | 0.211 | N | 0.754 | deleterious | N | 0.501860211 | None | None | N |
| V/H | 0.9946 | likely_pathogenic | 0.9925 | pathogenic | -2.503 | Highly Destabilizing | 0.935 | D | 0.819 | deleterious | None | None | None | None | N |
| V/I | 0.0622 | likely_benign | 0.0602 | benign | 0.07 | Stabilizing | None | N | 0.179 | neutral | N | 0.388994552 | None | None | N |
| V/K | 0.9895 | likely_pathogenic | 0.9871 | pathogenic | -1.13 | Destabilizing | 0.555 | D | 0.747 | deleterious | None | None | None | None | N |
| V/L | 0.1755 | likely_benign | 0.1489 | benign | 0.07 | Stabilizing | None | N | 0.227 | neutral | N | 0.331185894 | None | None | N |
| V/M | 0.3717 | ambiguous | 0.3036 | benign | -0.109 | Destabilizing | 0.38 | N | 0.611 | neutral | None | None | None | None | N |
| V/N | 0.9859 | likely_pathogenic | 0.9824 | pathogenic | -1.896 | Destabilizing | 0.791 | D | 0.807 | deleterious | None | None | None | None | N |
| V/P | 0.9827 | likely_pathogenic | 0.9771 | pathogenic | -0.504 | Destabilizing | 0.791 | D | 0.784 | deleterious | None | None | None | None | N |
| V/Q | 0.9839 | likely_pathogenic | 0.9805 | pathogenic | -1.429 | Destabilizing | 0.791 | D | 0.791 | deleterious | None | None | None | None | N |
| V/R | 0.9804 | likely_pathogenic | 0.9776 | pathogenic | -1.593 | Destabilizing | 0.555 | D | 0.809 | deleterious | None | None | None | None | N |
| V/S | 0.9598 | likely_pathogenic | 0.9497 | pathogenic | -2.289 | Highly Destabilizing | 0.262 | N | 0.695 | prob.neutral | None | None | None | None | N |
| V/T | 0.9059 | likely_pathogenic | 0.8852 | pathogenic | -1.784 | Destabilizing | 0.149 | N | 0.587 | neutral | None | None | None | None | N |
| V/W | 0.9902 | likely_pathogenic | 0.9852 | pathogenic | -1.501 | Destabilizing | 0.935 | D | 0.819 | deleterious | None | None | None | None | N |
| V/Y | 0.9611 | likely_pathogenic | 0.9441 | pathogenic | -1.12 | Destabilizing | 0.081 | N | 0.691 | prob.neutral | 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.