TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26683	80272;80273;80274	chr2:178566085;178566084;178566083	chr2:179430812;179430811;179430810
N2AB	25042	75349;75350;75351	chr2:178566085;178566084;178566083	chr2:179430812;179430811;179430810
N2A	24115	72568;72569;72570	chr2:178566085;178566084;178566083	chr2:179430812;179430811;179430810
N2B	17618	53077;53078;53079	chr2:178566085;178566084;178566083	chr2:179430812;179430811;179430810
Novex-1	17743	53452;53453;53454	chr2:178566085;178566084;178566083	chr2:179430812;179430811;179430810
Novex-2	17810	53653;53654;53655	chr2:178566085;178566084;178566083	chr2:179430812;179430811;179430810
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-82
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4167
• 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
T/A	rs1447655466	-0.891	0.976	N	0.489	0.308	0.20549828249	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.65948E-04
T/A	rs1447655466	-0.891	0.976	N	0.489	0.308	0.20549828249	gnomAD-4.0.0	5.47412E-06	None	None	None	None	I	None	2.98918E-05	0	None	0	0	None	0	0	5.39725E-06	0	1.65689E-05
T/P	None	None	0.998	N	0.648	0.513	0.256283259241	gnomAD-4.0.0	6.84265E-07	None	None	None	None	I	None	0	2.23624E-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	0.272	likely_benign	0.2418	benign	-0.812	Destabilizing	0.976	D	0.489	neutral	N	0.485008441	None	None	I
T/C	0.7626	likely_pathogenic	0.7325	pathogenic	-0.463	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
T/D	0.947	likely_pathogenic	0.9283	pathogenic	-0.057	Destabilizing	0.998	D	0.692	prob.delet.	None	None	None	None	I
T/E	0.8981	likely_pathogenic	0.8573	pathogenic	-0.118	Destabilizing	0.999	D	0.695	prob.delet.	None	None	None	None	I
T/F	0.8514	likely_pathogenic	0.7944	pathogenic	-1.245	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
T/G	0.6654	likely_pathogenic	0.6053	pathogenic	-0.959	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
T/H	0.787	likely_pathogenic	0.7328	pathogenic	-1.333	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
T/I	0.66	likely_pathogenic	0.5981	pathogenic	-0.528	Destabilizing	1.0	D	0.676	prob.neutral	N	0.50965617	None	None	I
T/K	0.7341	likely_pathogenic	0.6604	pathogenic	-0.524	Destabilizing	1.0	D	0.698	prob.delet.	None	None	None	None	I
T/L	0.4251	ambiguous	0.3892	ambiguous	-0.528	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
T/M	0.3072	likely_benign	0.2578	benign	-0.068	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	I
T/N	0.5511	ambiguous	0.4897	ambiguous	-0.324	Destabilizing	0.998	D	0.679	prob.neutral	N	0.468098376	None	None	I
T/P	0.4959	ambiguous	0.4858	ambiguous	-0.595	Destabilizing	0.998	D	0.648	neutral	N	0.478445041	None	None	I
T/Q	0.7324	likely_pathogenic	0.6637	pathogenic	-0.653	Destabilizing	0.999	D	0.67	prob.neutral	None	None	None	None	I
T/R	0.7266	likely_pathogenic	0.6447	pathogenic	-0.223	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
T/S	0.1783	likely_benign	0.172	benign	-0.612	Destabilizing	0.976	D	0.563	neutral	N	0.456131116	None	None	I
T/V	0.44	ambiguous	0.4001	ambiguous	-0.595	Destabilizing	0.998	D	0.661	prob.neutral	None	None	None	None	I
T/W	0.9742	likely_pathogenic	0.9626	pathogenic	-1.125	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	I
T/Y	0.8516	likely_pathogenic	0.7824	pathogenic	-0.888	Destabilizing	1.0	D	0.771	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.