Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26494 | 79705;79706;79707 | chr2:178566652;178566651;178566650 | chr2:179431379;179431378;179431377 |
| N2AB | 24853 | 74782;74783;74784 | chr2:178566652;178566651;178566650 | chr2:179431379;179431378;179431377 |
| N2A | 23926 | 72001;72002;72003 | chr2:178566652;178566651;178566650 | chr2:179431379;179431378;179431377 |
| N2B | 17429 | 52510;52511;52512 | chr2:178566652;178566651;178566650 | chr2:179431379;179431378;179431377 |
| Novex-1 | 17554 | 52885;52886;52887 | chr2:178566652;178566651;178566650 | chr2:179431379;179431378;179431377 |
| Novex-2 | 17621 | 53086;53087;53088 | chr2:178566652;178566651;178566650 | chr2:179431379;179431378;179431377 |
| 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/V | rs368484949  |
-0.052 | None | N | 0.377 | 0.043 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.04E-05 | 0 |
| A/V | rs368484949 |
-0.052 | None | N | 0.377 | 0.043 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| A/V | rs368484949 |
-0.052 | None | N | 0.377 | 0.043 | None | gnomAD-4.0.0 | 4.46435E-05 | None | None | None | None | I | None | 1.33533E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.59473E-05 | 0 | 8.0082E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3321 | likely_benign | 0.381 | ambiguous | -1.368 | Destabilizing | 0.824 | D | 0.657 | neutral | None | None | None | None | I |
| A/D | 0.8417 | likely_pathogenic | 0.8691 | pathogenic | -2.385 | Highly Destabilizing | 0.555 | D | 0.786 | deleterious | None | None | None | None | I |
| A/E | 0.7709 | likely_pathogenic | 0.8036 | pathogenic | -2.278 | Highly Destabilizing | 0.117 | N | 0.754 | deleterious | N | 0.470354826 | None | None | I |
| A/F | 0.4626 | ambiguous | 0.5062 | ambiguous | -0.926 | Destabilizing | 0.001 | N | 0.515 | neutral | None | None | None | None | I |
| A/G | 0.2056 | likely_benign | 0.1995 | benign | -1.45 | Destabilizing | 0.211 | N | 0.669 | neutral | N | 0.515459926 | None | None | I |
| A/H | 0.8073 | likely_pathogenic | 0.8518 | pathogenic | -1.889 | Destabilizing | 0.935 | D | 0.796 | deleterious | None | None | None | None | I |
| A/I | 0.1602 | likely_benign | 0.1773 | benign | -0.062 | Destabilizing | 0.029 | N | 0.718 | prob.delet. | None | None | None | None | I |
| A/K | 0.8696 | likely_pathogenic | 0.9021 | pathogenic | -1.326 | Destabilizing | 0.149 | N | 0.765 | deleterious | None | None | None | None | I |
| A/L | 0.1688 | likely_benign | 0.1927 | benign | -0.062 | Destabilizing | 0.035 | N | 0.65 | neutral | None | None | None | None | I |
| A/M | 0.234 | likely_benign | 0.2742 | benign | -0.26 | Destabilizing | 0.38 | N | 0.755 | deleterious | None | None | None | None | I |
| A/N | 0.5658 | likely_pathogenic | 0.6264 | pathogenic | -1.454 | Destabilizing | 0.791 | D | 0.804 | deleterious | None | None | None | None | I |
| A/P | 0.114 | likely_benign | 0.1197 | benign | -0.351 | Destabilizing | None | N | 0.443 | neutral | N | 0.318075816 | None | None | I |
| A/Q | 0.7276 | likely_pathogenic | 0.7798 | pathogenic | -1.417 | Destabilizing | 0.791 | D | 0.771 | deleterious | None | None | None | None | I |
| A/R | 0.8267 | likely_pathogenic | 0.8659 | pathogenic | -1.256 | Destabilizing | 0.555 | D | 0.773 | deleterious | None | None | None | None | I |
| A/S | 0.145 | likely_benign | 0.1536 | benign | -1.802 | Destabilizing | 0.117 | N | 0.692 | prob.neutral | N | 0.515286568 | None | None | I |
| A/T | 0.0975 | likely_benign | 0.1063 | benign | -1.588 | Destabilizing | 0.062 | N | 0.689 | prob.neutral | N | 0.504069497 | None | None | I |
| A/V | 0.0881 | likely_benign | 0.0926 | benign | -0.351 | Destabilizing | None | N | 0.377 | neutral | N | 0.421024039 | None | None | I |
| A/W | 0.8758 | likely_pathogenic | 0.9097 | pathogenic | -1.591 | Destabilizing | 0.935 | D | 0.809 | deleterious | None | None | None | None | I |
| A/Y | 0.6836 | likely_pathogenic | 0.7333 | pathogenic | -1.073 | Destabilizing | 0.235 | N | 0.795 | deleterious | None | None | None | None | I |
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.