TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17844	53755;53756;53757	chr2:178607072;178607071;178607070	chr2:179471799;179471798;179471797
N2AB	16203	48832;48833;48834	chr2:178607072;178607071;178607070	chr2:179471799;179471798;179471797
N2A	15276	46051;46052;46053	chr2:178607072;178607071;178607070	chr2:179471799;179471798;179471797
N2B	8779	26560;26561;26562	chr2:178607072;178607071;178607070	chr2:179471799;179471798;179471797
Novex-1	8904	26935;26936;26937	chr2:178607072;178607071;178607070	chr2:179471799;179471798;179471797
Novex-2	8971	27136;27137;27138	chr2:178607072;178607071;178607070	chr2:179471799;179471798;179471797
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-17
• Domain position: 81
• Structural Position: 115
• Q(SASA): 0.2245
• 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
G/S	rs748153885	-0.623	1.0	D	0.871	0.785	0.494974121195	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
G/S	rs748153885	-0.623	1.0	D	0.871	0.785	0.494974121195	gnomAD-4.0.0	1.59519E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86372E-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
G/A	0.9615	likely_pathogenic	0.9142	pathogenic	-0.647	Destabilizing	1.0	D	0.761	deleterious	D	0.546496327	None	None	I
G/C	0.9852	likely_pathogenic	0.963	pathogenic	-0.986	Destabilizing	1.0	D	0.877	deleterious	D	0.547763775	None	None	I
G/D	0.9904	likely_pathogenic	0.9809	pathogenic	-1.118	Destabilizing	1.0	D	0.925	deleterious	D	0.53590049	None	None	I
G/E	0.9964	likely_pathogenic	0.9916	pathogenic	-1.256	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
G/F	0.9974	likely_pathogenic	0.9939	pathogenic	-1.171	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
G/H	0.9963	likely_pathogenic	0.9924	pathogenic	-0.935	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/I	0.9973	likely_pathogenic	0.9914	pathogenic	-0.604	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
G/K	0.9974	likely_pathogenic	0.9947	pathogenic	-1.259	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	I
G/L	0.9956	likely_pathogenic	0.9896	pathogenic	-0.604	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/M	0.9987	likely_pathogenic	0.9967	pathogenic	-0.504	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
G/N	0.9933	likely_pathogenic	0.9883	pathogenic	-0.887	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
G/P	0.999	likely_pathogenic	0.9981	pathogenic	-0.582	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
G/Q	0.994	likely_pathogenic	0.9869	pathogenic	-1.197	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	I
G/R	0.9902	likely_pathogenic	0.9774	pathogenic	-0.722	Destabilizing	1.0	D	0.922	deleterious	D	0.535647001	None	None	I
G/S	0.941	likely_pathogenic	0.8781	pathogenic	-1.044	Destabilizing	1.0	D	0.871	deleterious	D	0.534886532	None	None	I
G/T	0.991	likely_pathogenic	0.9785	pathogenic	-1.12	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
G/V	0.9951	likely_pathogenic	0.9851	pathogenic	-0.582	Destabilizing	1.0	D	0.889	deleterious	D	0.546496327	None	None	I
G/W	0.9966	likely_pathogenic	0.991	pathogenic	-1.353	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
G/Y	0.9964	likely_pathogenic	0.9916	pathogenic	-1.028	Destabilizing	1.0	D	0.899	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.