Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22181 | 66766;66767;66768 | chr2:178581727;178581726;178581725 | chr2:179446454;179446453;179446452 |
| N2AB | 20540 | 61843;61844;61845 | chr2:178581727;178581726;178581725 | chr2:179446454;179446453;179446452 |
| N2A | 19613 | 59062;59063;59064 | chr2:178581727;178581726;178581725 | chr2:179446454;179446453;179446452 |
| N2B | 13116 | 39571;39572;39573 | chr2:178581727;178581726;178581725 | chr2:179446454;179446453;179446452 |
| Novex-1 | 13241 | 39946;39947;39948 | chr2:178581727;178581726;178581725 | chr2:179446454;179446453;179446452 |
| Novex-2 | 13308 | 40147;40148;40149 | chr2:178581727;178581726;178581725 | chr2:179446454;179446453;179446452 |
| 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/G | rs1187714227  |
-0.136 | 0.979 | N | 0.638 | 0.292 | 0.289847578895 | gnomAD-2.1.1 | 7.33E-06 | None | None | None | None | I | None | 4.23E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.05E-06 | 0 |
| A/G | rs1187714227 |
-0.136 | 0.979 | N | 0.638 | 0.292 | 0.289847578895 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/G | rs1187714227 |
-0.136 | 0.979 | N | 0.638 | 0.292 | 0.289847578895 | gnomAD-4.0.0 | 2.57455E-06 | None | None | None | None | I | None | 1.69302E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40316E-06 | 0 | 0 |
| A/T | None | None | 0.958 | N | 0.657 | 0.235 | 0.309839678437 | gnomAD-4.0.0 | 6.86036E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16583E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6805 | likely_pathogenic | 0.7076 | pathogenic | -0.803 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| A/D | 0.8801 | likely_pathogenic | 0.9213 | pathogenic | -0.473 | Destabilizing | 0.998 | D | 0.74 | deleterious | N | 0.452525956 | None | None | I |
| A/E | 0.8144 | likely_pathogenic | 0.8739 | pathogenic | -0.618 | Destabilizing | 0.995 | D | 0.745 | deleterious | None | None | None | None | I |
| A/F | 0.7377 | likely_pathogenic | 0.7618 | pathogenic | -0.851 | Destabilizing | 0.991 | D | 0.754 | deleterious | None | None | None | None | I |
| A/G | 0.3981 | ambiguous | 0.4463 | ambiguous | -0.319 | Destabilizing | 0.979 | D | 0.638 | neutral | N | 0.441348957 | None | None | I |
| A/H | 0.839 | likely_pathogenic | 0.8606 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| A/I | 0.4983 | ambiguous | 0.5353 | ambiguous | -0.348 | Destabilizing | 0.938 | D | 0.651 | neutral | None | None | None | None | I |
| A/K | 0.9071 | likely_pathogenic | 0.9347 | pathogenic | -0.658 | Destabilizing | 0.995 | D | 0.745 | deleterious | None | None | None | None | I |
| A/L | 0.3877 | ambiguous | 0.4054 | ambiguous | -0.348 | Destabilizing | 0.938 | D | 0.581 | neutral | None | None | None | None | I |
| A/M | 0.536 | ambiguous | 0.5465 | ambiguous | -0.525 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| A/N | 0.6809 | likely_pathogenic | 0.7159 | pathogenic | -0.353 | Destabilizing | 0.998 | D | 0.756 | deleterious | None | None | None | None | I |
| A/P | 0.5668 | likely_pathogenic | 0.6078 | pathogenic | -0.292 | Destabilizing | 0.998 | D | 0.731 | prob.delet. | N | 0.488177324 | None | None | I |
| A/Q | 0.7069 | likely_pathogenic | 0.7537 | pathogenic | -0.609 | Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | I |
| A/R | 0.8177 | likely_pathogenic | 0.8637 | pathogenic | -0.201 | Destabilizing | 0.995 | D | 0.736 | prob.delet. | None | None | None | None | I |
| A/S | 0.1826 | likely_benign | 0.1982 | benign | -0.544 | Destabilizing | 0.979 | D | 0.619 | neutral | N | 0.453160674 | None | None | I |
| A/T | 0.2565 | likely_benign | 0.2884 | benign | -0.61 | Destabilizing | 0.958 | D | 0.657 | neutral | N | 0.45891321 | None | None | I |
| A/V | 0.2945 | likely_benign | 0.3336 | benign | -0.292 | Destabilizing | 0.142 | N | 0.296 | neutral | N | 0.478885838 | None | None | I |
| A/W | 0.9425 | likely_pathogenic | 0.9555 | pathogenic | -0.989 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| A/Y | 0.8219 | likely_pathogenic | 0.842 | pathogenic | -0.654 | Destabilizing | 0.995 | D | 0.751 | 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.