Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25185 | 75778;75779;75780 | chr2:178570579;178570578;178570577 | chr2:179435306;179435305;179435304 |
| N2AB | 23544 | 70855;70856;70857 | chr2:178570579;178570578;178570577 | chr2:179435306;179435305;179435304 |
| N2A | 22617 | 68074;68075;68076 | chr2:178570579;178570578;178570577 | chr2:179435306;179435305;179435304 |
| N2B | 16120 | 48583;48584;48585 | chr2:178570579;178570578;178570577 | chr2:179435306;179435305;179435304 |
| Novex-1 | 16245 | 48958;48959;48960 | chr2:178570579;178570578;178570577 | chr2:179435306;179435305;179435304 |
| Novex-2 | 16312 | 49159;49160;49161 | chr2:178570579;178570578;178570577 | chr2:179435306;179435305;179435304 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/T | rs371042435  |
-1.442 | 0.001 | N | 0.288 | 0.228 | None | gnomAD-2.1.1 | 1.08826E-04 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 8.4984E-04 | None | 0 | 0 | 0 |
| K/T | rs371042435 |
-1.442 | 0.001 | N | 0.288 | 0.228 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14079E-04 | 0 |
| K/T | rs371042435 |
-1.442 | 0.001 | N | 0.288 | 0.228 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| K/T | rs371042435 |
-1.442 | 0.001 | N | 0.288 | 0.228 | None | gnomAD-4.0.0 | 3.96671E-05 | None | None | None | None | N | None | 3.99957E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.6977E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.2986 | likely_benign | 0.3528 | ambiguous | -0.816 | Destabilizing | 0.103 | N | 0.396 | neutral | None | None | None | None | N |
| K/C | 0.4321 | ambiguous | 0.4866 | ambiguous | -1.027 | Destabilizing | 0.965 | D | 0.611 | neutral | None | None | None | None | N |
| K/D | 0.671 | likely_pathogenic | 0.7172 | pathogenic | -0.495 | Destabilizing | 0.561 | D | 0.535 | neutral | None | None | None | None | N |
| K/E | 0.1743 | likely_benign | 0.1951 | benign | -0.339 | Destabilizing | 0.285 | N | 0.422 | neutral | N | 0.490154129 | None | None | N |
| K/F | 0.5282 | ambiguous | 0.586 | pathogenic | -0.35 | Destabilizing | 0.818 | D | 0.643 | neutral | None | None | None | None | N |
| K/G | 0.5609 | ambiguous | 0.624 | pathogenic | -1.224 | Destabilizing | 0.209 | N | 0.515 | neutral | None | None | None | None | N |
| K/H | 0.1781 | likely_benign | 0.1978 | benign | -1.501 | Destabilizing | 0.965 | D | 0.553 | neutral | None | None | None | None | N |
| K/I | 0.1494 | likely_benign | 0.168 | benign | 0.266 | Stabilizing | 0.209 | N | 0.515 | neutral | None | None | None | None | N |
| K/L | 0.1607 | likely_benign | 0.1839 | benign | 0.266 | Stabilizing | 0.001 | N | 0.417 | neutral | None | None | None | None | N |
| K/M | 0.1178 | likely_benign | 0.1304 | benign | 0.062 | Stabilizing | 0.772 | D | 0.57 | neutral | N | 0.510473473 | None | None | N |
| K/N | 0.3625 | ambiguous | 0.4012 | ambiguous | -0.891 | Destabilizing | 0.491 | N | 0.461 | neutral | N | 0.50287271 | None | None | N |
| K/P | 0.9625 | likely_pathogenic | 0.9706 | pathogenic | -0.066 | Destabilizing | 0.722 | D | 0.556 | neutral | None | None | None | None | N |
| K/Q | 0.1084 | likely_benign | 0.1166 | benign | -0.902 | Destabilizing | 0.491 | N | 0.535 | neutral | N | 0.491442208 | None | None | N |
| K/R | 0.0798 | likely_benign | 0.0839 | benign | -0.856 | Destabilizing | 0.491 | N | 0.432 | neutral | N | 0.472645804 | None | None | N |
| K/S | 0.3409 | ambiguous | 0.3943 | ambiguous | -1.577 | Destabilizing | 0.007 | N | 0.217 | neutral | None | None | None | None | N |
| K/T | 0.0946 | likely_benign | 0.1063 | benign | -1.196 | Destabilizing | 0.001 | N | 0.288 | neutral | N | 0.432529977 | None | None | N |
| K/V | 0.1523 | likely_benign | 0.1752 | benign | -0.066 | Destabilizing | 0.209 | N | 0.545 | neutral | None | None | None | None | N |
| K/W | 0.5677 | likely_pathogenic | 0.6227 | pathogenic | -0.217 | Destabilizing | 0.991 | D | 0.626 | neutral | None | None | None | None | N |
| K/Y | 0.4271 | ambiguous | 0.4782 | ambiguous | 0.09 | Stabilizing | 0.901 | D | 0.641 | 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.