TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21186	63781;63782;63783	chr2:178587753;178587752;178587751	chr2:179452480;179452479;179452478
N2AB	19545	58858;58859;58860	chr2:178587753;178587752;178587751	chr2:179452480;179452479;179452478
N2A	18618	56077;56078;56079	chr2:178587753;178587752;178587751	chr2:179452480;179452479;179452478
N2B	12121	36586;36587;36588	chr2:178587753;178587752;178587751	chr2:179452480;179452479;179452478
Novex-1	12246	36961;36962;36963	chr2:178587753;178587752;178587751	chr2:179452480;179452479;179452478
Novex-2	12313	37162;37163;37164	chr2:178587753;178587752;178587751	chr2:179452480;179452479;179452478
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-123
• Domain position: 10
• Structural Position: 16
• Q(SASA): 0.1712
• 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/M	None	None	0.942	D	0.547	0.604	0.695291002561	gnomAD-4.0.0	6.85778E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16417E-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
V/A	0.6119	likely_pathogenic	0.62	pathogenic	-1.876	Destabilizing	0.489	N	0.495	neutral	D	0.538641509	None	None	I
V/C	0.8633	likely_pathogenic	0.8747	pathogenic	-1.412	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	I
V/D	0.9852	likely_pathogenic	0.9826	pathogenic	-2.031	Highly Destabilizing	0.956	D	0.675	prob.neutral	None	None	None	None	I
V/E	0.9408	likely_pathogenic	0.9373	pathogenic	-1.94	Destabilizing	0.97	D	0.621	neutral	D	0.551968781	None	None	I
V/F	0.7717	likely_pathogenic	0.7125	pathogenic	-1.276	Destabilizing	0.956	D	0.625	neutral	None	None	None	None	I
V/G	0.8004	likely_pathogenic	0.7945	pathogenic	-2.293	Highly Destabilizing	0.014	N	0.473	neutral	D	0.536573551	None	None	I
V/H	0.977	likely_pathogenic	0.9748	pathogenic	-1.91	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	I
V/I	0.1353	likely_benign	0.1308	benign	-0.783	Destabilizing	0.559	D	0.507	neutral	None	None	None	None	I
V/K	0.9515	likely_pathogenic	0.949	pathogenic	-1.647	Destabilizing	0.956	D	0.616	neutral	None	None	None	None	I
V/L	0.6632	likely_pathogenic	0.649	pathogenic	-0.783	Destabilizing	0.014	N	0.254	neutral	D	0.540740452	None	None	I
V/M	0.6261	likely_pathogenic	0.6056	pathogenic	-0.69	Destabilizing	0.942	D	0.547	neutral	D	0.544713853	None	None	I
V/N	0.9479	likely_pathogenic	0.9451	pathogenic	-1.638	Destabilizing	0.956	D	0.679	prob.neutral	None	None	None	None	I
V/P	0.985	likely_pathogenic	0.9857	pathogenic	-1.115	Destabilizing	0.993	D	0.625	neutral	None	None	None	None	I
V/Q	0.8921	likely_pathogenic	0.886	pathogenic	-1.684	Destabilizing	0.993	D	0.627	neutral	None	None	None	None	I
V/R	0.9156	likely_pathogenic	0.9078	pathogenic	-1.23	Destabilizing	0.978	D	0.683	prob.neutral	None	None	None	None	I
V/S	0.8034	likely_pathogenic	0.794	pathogenic	-2.223	Highly Destabilizing	0.956	D	0.619	neutral	None	None	None	None	I
V/T	0.6193	likely_pathogenic	0.6275	pathogenic	-2.012	Highly Destabilizing	0.926	D	0.54	neutral	None	None	None	None	I
V/W	0.995	likely_pathogenic	0.994	pathogenic	-1.616	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	I
V/Y	0.966	likely_pathogenic	0.9588	pathogenic	-1.29	Destabilizing	0.993	D	0.608	neutral	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.