TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8750	26473;26474;26475	chr2:178714526;178714525;178714524	chr2:179579253;179579252;179579251
N2AB	8433	25522;25523;25524	chr2:178714526;178714525;178714524	chr2:179579253;179579252;179579251
N2A	7506	22741;22742;22743	chr2:178714526;178714525;178714524	chr2:179579253;179579252;179579251
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-73
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.375
• Predicted PPI site: I

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
G/C	rs757423560	-0.635	0.983	D	0.781	0.622	0.850572185047	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
G/C	rs757423560	-0.635	0.983	D	0.781	0.622	0.850572185047	gnomAD-4.0.0	6.84531E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16077E-05	0
G/S	None	None	0.139	D	0.718	0.514	0.403609169532	gnomAD-4.0.0	6.84531E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65761E-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
G/A	0.2425	likely_benign	0.3566	ambiguous	-0.457	Destabilizing	0.01	N	0.355	neutral	D	0.651453561	None	None	I
G/C	0.4003	ambiguous	0.5303	ambiguous	-0.897	Destabilizing	0.983	D	0.781	deleterious	D	0.652058973	None	None	I
G/D	0.1499	likely_benign	0.2091	benign	-0.839	Destabilizing	0.005	N	0.471	neutral	D	0.604567019	None	None	I
G/E	0.1924	likely_benign	0.2916	benign	-0.985	Destabilizing	0.81	D	0.779	deleterious	None	None	None	None	I
G/F	0.6707	likely_pathogenic	0.7944	pathogenic	-1.019	Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	I
G/H	0.4202	ambiguous	0.5561	ambiguous	-0.757	Destabilizing	0.985	D	0.795	deleterious	None	None	None	None	I
G/I	0.5957	likely_pathogenic	0.7778	pathogenic	-0.473	Destabilizing	0.945	D	0.793	deleterious	None	None	None	None	I
G/K	0.4064	ambiguous	0.5846	pathogenic	-1.133	Destabilizing	0.895	D	0.781	deleterious	None	None	None	None	I
G/L	0.5191	ambiguous	0.6714	pathogenic	-0.473	Destabilizing	0.895	D	0.763	deleterious	None	None	None	None	I
G/M	0.6152	likely_pathogenic	0.7601	pathogenic	-0.474	Destabilizing	0.995	D	0.782	deleterious	None	None	None	None	I
G/N	0.2263	likely_benign	0.3002	benign	-0.743	Destabilizing	0.81	D	0.781	deleterious	None	None	None	None	I
G/P	0.8873	likely_pathogenic	0.9399	pathogenic	-0.432	Destabilizing	0.866	D	0.803	deleterious	None	None	None	None	I
G/Q	0.3007	likely_benign	0.4335	ambiguous	-1.03	Destabilizing	0.895	D	0.807	deleterious	None	None	None	None	I
G/R	0.3021	likely_benign	0.4466	ambiguous	-0.636	Destabilizing	0.866	D	0.809	deleterious	D	0.635403839	None	None	I
G/S	0.1283	likely_benign	0.1742	benign	-0.889	Destabilizing	0.139	N	0.718	prob.delet.	D	0.605979649	None	None	I
G/T	0.2909	likely_benign	0.4229	ambiguous	-0.97	Destabilizing	0.895	D	0.788	deleterious	None	None	None	None	I
G/V	0.4747	ambiguous	0.6664	pathogenic	-0.432	Destabilizing	0.866	D	0.764	deleterious	D	0.651857169	None	None	I
G/W	0.446	ambiguous	0.5694	pathogenic	-1.21	Destabilizing	0.995	D	0.776	deleterious	None	None	None	None	I
G/Y	0.5207	ambiguous	0.6595	pathogenic	-0.874	Destabilizing	0.995	D	0.803	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.