Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31503 | 94732;94733;94734 | chr2:178547018;178547017;178547016 | chr2:179411745;179411744;179411743 |
| N2AB | 29862 | 89809;89810;89811 | chr2:178547018;178547017;178547016 | chr2:179411745;179411744;179411743 |
| N2A | 28935 | 87028;87029;87030 | chr2:178547018;178547017;178547016 | chr2:179411745;179411744;179411743 |
| N2B | 22438 | 67537;67538;67539 | chr2:178547018;178547017;178547016 | chr2:179411745;179411744;179411743 |
| Novex-1 | 22563 | 67912;67913;67914 | chr2:178547018;178547017;178547016 | chr2:179411745;179411744;179411743 |
| Novex-2 | 22630 | 68113;68114;68115 | chr2:178547018;178547017;178547016 | chr2:179411745;179411744;179411743 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs375657115  |
-1.946 | 1.0 | N | 0.787 | 0.336 | None | gnomAD-2.1.1 | 5.04E-05 | None | None | None | None | N | None | 0 | 1.14116E-04 | None | 0 | 0 | None | 0 | None | 0 | 7.1E-05 | 1.41924E-04 |
| A/T | rs375657115 |
-1.946 | 1.0 | N | 0.787 | 0.336 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 1.96592E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 9.56023E-04 |
| A/T | rs375657115 |
-1.946 | 1.0 | N | 0.787 | 0.336 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/T | rs375657115 |
-1.946 | 1.0 | N | 0.787 | 0.336 | None | gnomAD-4.0.0 | 5.28468E-05 | None | None | None | None | N | None | 1.33683E-05 | 1.67616E-04 | None | 0 | 0 | None | 0 | 1.65893E-04 | 5.35643E-05 | 0 | 1.60705E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8374 | likely_pathogenic | 0.79 | pathogenic | -1.801 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| A/D | 0.9987 | likely_pathogenic | 0.9991 | pathogenic | -3.082 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | D | 0.537883548 | None | None | N |
| A/E | 0.9967 | likely_pathogenic | 0.9976 | pathogenic | -2.904 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| A/F | 0.991 | likely_pathogenic | 0.9918 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| A/G | 0.6994 | likely_pathogenic | 0.6943 | pathogenic | -1.738 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.500029197 | None | None | N |
| A/H | 0.9981 | likely_pathogenic | 0.9983 | pathogenic | -1.88 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| A/I | 0.9206 | likely_pathogenic | 0.9153 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| A/K | 0.9991 | likely_pathogenic | 0.9994 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| A/L | 0.8245 | likely_pathogenic | 0.8094 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| A/M | 0.9464 | likely_pathogenic | 0.9396 | pathogenic | -0.781 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| A/N | 0.993 | likely_pathogenic | 0.9932 | pathogenic | -1.824 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| A/P | 0.908 | likely_pathogenic | 0.9055 | pathogenic | -0.587 | Destabilizing | 1.0 | D | 0.799 | deleterious | N | 0.4767567 | None | None | N |
| A/Q | 0.9928 | likely_pathogenic | 0.994 | pathogenic | -1.671 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| A/R | 0.9952 | likely_pathogenic | 0.9967 | pathogenic | -1.387 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| A/S | 0.5593 | ambiguous | 0.4955 | ambiguous | -2.112 | Highly Destabilizing | 0.999 | D | 0.621 | neutral | N | 0.502889579 | None | None | N |
| A/T | 0.8523 | likely_pathogenic | 0.7836 | pathogenic | -1.833 | Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.479265142 | None | None | N |
| A/V | 0.7489 | likely_pathogenic | 0.7153 | pathogenic | -0.587 | Destabilizing | 0.999 | D | 0.689 | prob.delet. | N | 0.482063072 | None | None | N |
| A/W | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -1.459 | Destabilizing | 1.0 | D | 0.721 | deleterious | None | None | None | None | N |
| A/Y | 0.9966 | likely_pathogenic | 0.9973 | pathogenic | -1.027 | Destabilizing | 1.0 | D | 0.808 | 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.