TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27687	83284;83285;83286	chr2:178563073;178563072;178563071	chr2:179427800;179427799;179427798
N2AB	26046	78361;78362;78363	chr2:178563073;178563072;178563071	chr2:179427800;179427799;179427798
N2A	25119	75580;75581;75582	chr2:178563073;178563072;178563071	chr2:179427800;179427799;179427798
N2B	18622	56089;56090;56091	chr2:178563073;178563072;178563071	chr2:179427800;179427799;179427798
Novex-1	18747	56464;56465;56466	chr2:178563073;178563072;178563071	chr2:179427800;179427799;179427798
Novex-2	18814	56665;56666;56667	chr2:178563073;178563072;178563071	chr2:179427800;179427799;179427798
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-141
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1912
• 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
L/V	None	None	0.001	N	0.127	0.077	0.483224754729	gnomAD-4.0.0	6.84239E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99517E-07	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
L/A	0.5245	ambiguous	0.5855	pathogenic	-1.893	Destabilizing	0.373	N	0.384	neutral	None	None	None	None	I
L/C	0.6644	likely_pathogenic	0.6805	pathogenic	-1.241	Destabilizing	0.996	D	0.489	neutral	None	None	None	None	I
L/D	0.9845	likely_pathogenic	0.9839	pathogenic	-1.416	Destabilizing	0.984	D	0.539	neutral	None	None	None	None	I
L/E	0.9048	likely_pathogenic	0.9054	pathogenic	-1.282	Destabilizing	0.953	D	0.545	neutral	None	None	None	None	I
L/F	0.5684	likely_pathogenic	0.5585	ambiguous	-1.033	Destabilizing	0.91	D	0.513	neutral	None	None	None	None	I
L/G	0.8745	likely_pathogenic	0.8956	pathogenic	-2.349	Highly Destabilizing	0.953	D	0.545	neutral	None	None	None	None	I
L/H	0.8201	likely_pathogenic	0.8173	pathogenic	-1.621	Destabilizing	0.996	D	0.512	neutral	None	None	None	None	I
L/I	0.0911	likely_benign	0.0999	benign	-0.647	Destabilizing	0.016	N	0.137	neutral	None	None	None	None	I
L/K	0.8626	likely_pathogenic	0.8599	pathogenic	-1.432	Destabilizing	0.953	D	0.497	neutral	None	None	None	None	I
L/M	0.1914	likely_benign	0.1967	benign	-0.587	Destabilizing	0.939	D	0.531	neutral	N	0.521207755	None	None	I
L/N	0.8716	likely_pathogenic	0.885	pathogenic	-1.517	Destabilizing	0.984	D	0.555	neutral	None	None	None	None	I
L/P	0.9597	likely_pathogenic	0.9662	pathogenic	-1.035	Destabilizing	0.979	D	0.541	neutral	N	0.489886746	None	None	I
L/Q	0.6481	likely_pathogenic	0.6701	pathogenic	-1.483	Destabilizing	0.979	D	0.499	neutral	D	0.535291773	None	None	I
L/R	0.8043	likely_pathogenic	0.802	pathogenic	-1.052	Destabilizing	0.939	D	0.504	neutral	D	0.535118414	None	None	I
L/S	0.7491	likely_pathogenic	0.782	pathogenic	-2.24	Highly Destabilizing	0.854	D	0.478	neutral	None	None	None	None	I
L/T	0.4686	ambiguous	0.5171	ambiguous	-1.97	Destabilizing	0.742	D	0.417	neutral	None	None	None	None	I
L/V	0.0872	likely_benign	0.0958	benign	-1.035	Destabilizing	0.001	N	0.127	neutral	N	0.357871929	None	None	I
L/W	0.8833	likely_pathogenic	0.8679	pathogenic	-1.275	Destabilizing	0.996	D	0.489	neutral	None	None	None	None	I
L/Y	0.8814	likely_pathogenic	0.8738	pathogenic	-0.987	Destabilizing	0.953	D	0.511	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.