TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27587	82984;82985;82986	chr2:178563373;178563372;178563371	chr2:179428100;179428099;179428098
N2AB	25946	78061;78062;78063	chr2:178563373;178563372;178563371	chr2:179428100;179428099;179428098
N2A	25019	75280;75281;75282	chr2:178563373;178563372;178563371	chr2:179428100;179428099;179428098
N2B	18522	55789;55790;55791	chr2:178563373;178563372;178563371	chr2:179428100;179428099;179428098
Novex-1	18647	56164;56165;56166	chr2:178563373;178563372;178563371	chr2:179428100;179428099;179428098
Novex-2	18714	56365;56366;56367	chr2:178563373;178563372;178563371	chr2:179428100;179428099;179428098
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-89
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1153
• 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	rs876658085	None	0.773	N	0.54	0.132	0.419090007872	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	0.5455	ambiguous	0.5478	ambiguous	-2.279	Highly Destabilizing	0.025	N	0.347	neutral	N	0.504803002	None	None	N
V/C	0.8871	likely_pathogenic	0.8914	pathogenic	-2.883	Highly Destabilizing	0.997	D	0.814	deleterious	None	None	None	None	N
V/D	0.996	likely_pathogenic	0.995	pathogenic	-2.913	Highly Destabilizing	0.983	D	0.873	deleterious	D	0.54098201	None	None	N
V/E	0.9877	likely_pathogenic	0.9867	pathogenic	-2.663	Highly Destabilizing	0.975	D	0.854	deleterious	None	None	None	None	N
V/F	0.6662	likely_pathogenic	0.6357	pathogenic	-1.613	Destabilizing	0.983	D	0.834	deleterious	N	0.508986554	None	None	N
V/G	0.8826	likely_pathogenic	0.8573	pathogenic	-2.802	Highly Destabilizing	0.935	D	0.802	deleterious	N	0.521863797	None	None	N
V/H	0.9937	likely_pathogenic	0.9928	pathogenic	-2.555	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
V/I	0.0786	likely_benign	0.0861	benign	-0.782	Destabilizing	0.773	D	0.54	neutral	N	0.451603236	None	None	N
V/K	0.9911	likely_pathogenic	0.9895	pathogenic	-1.889	Destabilizing	0.975	D	0.862	deleterious	None	None	None	None	N
V/L	0.4567	ambiguous	0.4281	ambiguous	-0.782	Destabilizing	0.63	D	0.617	neutral	N	0.51199276	None	None	N
V/M	0.4709	ambiguous	0.471	ambiguous	-1.442	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	N
V/N	0.9806	likely_pathogenic	0.9792	pathogenic	-2.408	Highly Destabilizing	0.987	D	0.878	deleterious	None	None	None	None	N
V/P	0.9957	likely_pathogenic	0.9931	pathogenic	-1.261	Destabilizing	0.987	D	0.867	deleterious	None	None	None	None	N
V/Q	0.9817	likely_pathogenic	0.9801	pathogenic	-2.2	Highly Destabilizing	0.987	D	0.867	deleterious	None	None	None	None	N
V/R	0.9804	likely_pathogenic	0.977	pathogenic	-1.837	Destabilizing	0.987	D	0.875	deleterious	None	None	None	None	N
V/S	0.8902	likely_pathogenic	0.8872	pathogenic	-3.068	Highly Destabilizing	0.95	D	0.823	deleterious	None	None	None	None	N
V/T	0.799	likely_pathogenic	0.8045	pathogenic	-2.657	Highly Destabilizing	0.916	D	0.675	neutral	None	None	None	None	N
V/W	0.9944	likely_pathogenic	0.9929	pathogenic	-1.932	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9661	likely_pathogenic	0.9611	pathogenic	-1.647	Destabilizing	0.996	D	0.842	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.