TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29683	89272;89273;89274	chr2:178554064;178554063;178554062	chr2:179418791;179418790;179418789
N2AB	28042	84349;84350;84351	chr2:178554064;178554063;178554062	chr2:179418791;179418790;179418789
N2A	27115	81568;81569;81570	chr2:178554064;178554063;178554062	chr2:179418791;179418790;179418789
N2B	20618	62077;62078;62079	chr2:178554064;178554063;178554062	chr2:179418791;179418790;179418789
Novex-1	20743	62452;62453;62454	chr2:178554064;178554063;178554062	chr2:179418791;179418790;179418789
Novex-2	20810	62653;62654;62655	chr2:178554064;178554063;178554062	chr2:179418791;179418790;179418789
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-104
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.157
• 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
V/I	rs749433506	-0.376	0.997	N	0.478	0.24	0.566263476786	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	2.9E-05	None	0	1.66926E-04	None	0	None	0	0	0
V/I	rs749433506	-0.376	0.997	N	0.478	0.24	0.566263476786	gnomAD-4.0.0	4.7735E-06	None	None	None	None	I	None	0	2.28634E-05	None	0	5.5457E-05	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
V/A	0.3658	ambiguous	0.4456	ambiguous	-1.204	Destabilizing	0.999	D	0.547	neutral	N	0.50120255	None	None	I
V/C	0.7631	likely_pathogenic	0.7916	pathogenic	-1.039	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
V/D	0.9131	likely_pathogenic	0.9533	pathogenic	-0.974	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
V/E	0.8622	likely_pathogenic	0.9175	pathogenic	-0.936	Destabilizing	1.0	D	0.775	deleterious	N	0.488896246	None	None	I
V/F	0.4386	ambiguous	0.5731	pathogenic	-0.755	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
V/G	0.5329	ambiguous	0.6265	pathogenic	-1.538	Destabilizing	1.0	D	0.777	deleterious	N	0.507096769	None	None	I
V/H	0.9277	likely_pathogenic	0.9567	pathogenic	-0.972	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/I	0.0998	likely_benign	0.1096	benign	-0.384	Destabilizing	0.997	D	0.478	neutral	N	0.517596154	None	None	I
V/K	0.9361	likely_pathogenic	0.9628	pathogenic	-1.177	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
V/L	0.3931	ambiguous	0.5084	ambiguous	-0.384	Destabilizing	0.997	D	0.533	neutral	N	0.500087829	None	None	I
V/M	0.3577	ambiguous	0.451	ambiguous	-0.495	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
V/N	0.7563	likely_pathogenic	0.8384	pathogenic	-1.135	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/P	0.8749	likely_pathogenic	0.9115	pathogenic	-0.622	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
V/Q	0.8664	likely_pathogenic	0.9111	pathogenic	-1.197	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
V/R	0.9167	likely_pathogenic	0.9506	pathogenic	-0.746	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/S	0.5929	likely_pathogenic	0.697	pathogenic	-1.656	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
V/T	0.5054	ambiguous	0.5664	pathogenic	-1.493	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
V/W	0.9716	likely_pathogenic	0.986	pathogenic	-0.973	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
V/Y	0.8534	likely_pathogenic	0.9132	pathogenic	-0.654	Destabilizing	1.0	D	0.81	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.