TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14048	42367;42368;42369	chr2:178634732;178634731;178634730	chr2:179499459;179499458;179499457
N2AB	12407	37444;37445;37446	chr2:178634732;178634731;178634730	chr2:179499459;179499458;179499457
N2A	11480	34663;34664;34665	chr2:178634732;178634731;178634730	chr2:179499459;179499458;179499457
N2B	4983	15172;15173;15174	chr2:178634732;178634731;178634730	chr2:179499459;179499458;179499457
Novex-1	5108	15547;15548;15549	chr2:178634732;178634731;178634730	chr2:179499459;179499458;179499457
Novex-2	5175	15748;15749;15750	chr2:178634732;178634731;178634730	chr2:179499459;179499458;179499457
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-90
• Domain position: 84
• Structural Position: 171
• Q(SASA): 0.3339
• Predicted PPI site: N

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
T/I	rs1362774927	0.145	0.524	N	0.369	0.229	0.227260227426	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
T/I	rs1362774927	0.145	0.524	N	0.369	0.229	0.227260227426	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	2.28927E-05	None	0	0	None	0	0	0	0	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
T/A	0.3618	ambiguous	0.2633	benign	-0.792	Destabilizing	0.688	D	0.354	neutral	N	0.473143168	None	None	N
T/C	0.867	likely_pathogenic	0.8079	pathogenic	-0.558	Destabilizing	0.998	D	0.331	neutral	None	None	None	None	N
T/D	0.8355	likely_pathogenic	0.7373	pathogenic	0.002	Stabilizing	0.994	D	0.375	neutral	None	None	None	None	N
T/E	0.658	likely_pathogenic	0.5506	ambiguous	0.019	Stabilizing	0.994	D	0.38	neutral	None	None	None	None	N
T/F	0.7329	likely_pathogenic	0.5765	pathogenic	-0.78	Destabilizing	0.022	N	0.384	neutral	None	None	None	None	N
T/G	0.7994	likely_pathogenic	0.6803	pathogenic	-1.066	Destabilizing	0.978	D	0.466	neutral	None	None	None	None	N
T/H	0.4716	ambiguous	0.3325	benign	-1.313	Destabilizing	0.998	D	0.498	neutral	None	None	None	None	N
T/I	0.5825	likely_pathogenic	0.468	ambiguous	-0.153	Destabilizing	0.524	D	0.369	neutral	N	0.431176558	None	None	N
T/K	0.494	ambiguous	0.355	ambiguous	-0.664	Destabilizing	0.971	D	0.368	neutral	N	0.440243959	None	None	N
T/L	0.3877	ambiguous	0.299	benign	-0.153	Destabilizing	0.009	N	0.221	neutral	None	None	None	None	N
T/M	0.2578	likely_benign	0.1956	benign	0.003	Stabilizing	0.961	D	0.333	neutral	None	None	None	None	N
T/N	0.3208	likely_benign	0.2214	benign	-0.621	Destabilizing	0.994	D	0.374	neutral	None	None	None	None	N
T/P	0.9488	likely_pathogenic	0.9016	pathogenic	-0.333	Destabilizing	0.991	D	0.374	neutral	N	0.475745362	None	None	N
T/Q	0.4182	ambiguous	0.3229	benign	-0.742	Destabilizing	0.994	D	0.385	neutral	None	None	None	None	N
T/R	0.4616	ambiguous	0.319	benign	-0.506	Destabilizing	0.991	D	0.369	neutral	N	0.439881978	None	None	N
T/S	0.3667	ambiguous	0.2609	benign	-0.949	Destabilizing	0.915	D	0.439	neutral	N	0.472378188	None	None	N
T/V	0.4264	ambiguous	0.3529	ambiguous	-0.333	Destabilizing	0.087	N	0.122	neutral	None	None	None	None	N
T/W	0.917	likely_pathogenic	0.8477	pathogenic	-0.703	Destabilizing	0.998	D	0.526	neutral	None	None	None	None	N
T/Y	0.708	likely_pathogenic	0.5478	ambiguous	-0.468	Destabilizing	0.925	D	0.527	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.