TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25618	77077;77078;77079	chr2:178569280;178569279;178569278	chr2:179434007;179434006;179434005
N2AB	23977	72154;72155;72156	chr2:178569280;178569279;178569278	chr2:179434007;179434006;179434005
N2A	23050	69373;69374;69375	chr2:178569280;178569279;178569278	chr2:179434007;179434006;179434005
N2B	16553	49882;49883;49884	chr2:178569280;178569279;178569278	chr2:179434007;179434006;179434005
Novex-1	16678	50257;50258;50259	chr2:178569280;178569279;178569278	chr2:179434007;179434006;179434005
Novex-2	16745	50458;50459;50460	chr2:178569280;178569279;178569278	chr2:179434007;179434006;179434005
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: Fn3-74
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0775
• 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
V/I	None	None	0.998	N	0.531	0.263	0.446510307777	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.2904	likely_benign	0.3425	ambiguous	-2.347	Highly Destabilizing	1.0	D	0.642	neutral	N	0.479040553	None	None	N
V/C	0.8095	likely_pathogenic	0.8381	pathogenic	-2.11	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/D	0.9966	likely_pathogenic	0.9976	pathogenic	-3.033	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/E	0.9914	likely_pathogenic	0.9929	pathogenic	-2.716	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.535550733	None	None	N
V/F	0.7546	likely_pathogenic	0.7774	pathogenic	-1.385	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/G	0.7728	likely_pathogenic	0.8112	pathogenic	-2.975	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.546907039	None	None	N
V/H	0.9956	likely_pathogenic	0.9966	pathogenic	-2.82	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/I	0.0972	likely_benign	0.103	benign	-0.534	Destabilizing	0.998	D	0.531	neutral	N	0.508203093	None	None	N
V/K	0.9939	likely_pathogenic	0.9949	pathogenic	-1.848	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/L	0.373	ambiguous	0.4371	ambiguous	-0.534	Destabilizing	0.995	D	0.635	neutral	N	0.467454764	None	None	N
V/M	0.4305	ambiguous	0.4661	ambiguous	-0.93	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/N	0.9818	likely_pathogenic	0.9867	pathogenic	-2.497	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/P	0.9959	likely_pathogenic	0.9971	pathogenic	-1.118	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Q	0.9847	likely_pathogenic	0.9873	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/R	0.9857	likely_pathogenic	0.9883	pathogenic	-1.954	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/S	0.8052	likely_pathogenic	0.8474	pathogenic	-3.117	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/T	0.6244	likely_pathogenic	0.6871	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
V/W	0.9976	likely_pathogenic	0.9982	pathogenic	-1.874	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/Y	0.9804	likely_pathogenic	0.9844	pathogenic	-1.543	Destabilizing	1.0	D	0.867	deleterious	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.