TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20912	62959;62960;62961	chr2:178588991;178588990;178588989	chr2:179453718;179453717;179453716
N2AB	19271	58036;58037;58038	chr2:178588991;178588990;178588989	chr2:179453718;179453717;179453716
N2A	18344	55255;55256;55257	chr2:178588991;178588990;178588989	chr2:179453718;179453717;179453716
N2B	11847	35764;35765;35766	chr2:178588991;178588990;178588989	chr2:179453718;179453717;179453716
Novex-1	11972	36139;36140;36141	chr2:178588991;178588990;178588989	chr2:179453718;179453717;179453716
Novex-2	12039	36340;36341;36342	chr2:178588991;178588990;178588989	chr2:179453718;179453717;179453716
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-39
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4969
• 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
S/F	rs2049657792	None	0.991	N	0.688	0.405	0.721781199316	gnomAD-4.0.0	2.74014E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59928E-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
S/A	0.1903	likely_benign	0.2208	benign	-0.701	Destabilizing	0.76	D	0.409	neutral	N	0.49970104	None	None	I
S/C	0.339	likely_benign	0.39	ambiguous	-0.524	Destabilizing	0.999	D	0.681	prob.neutral	N	0.501349551	None	None	I
S/D	0.9384	likely_pathogenic	0.9505	pathogenic	-0.003	Destabilizing	0.953	D	0.541	neutral	None	None	None	None	I
S/E	0.9464	likely_pathogenic	0.9533	pathogenic	-0.044	Destabilizing	0.953	D	0.542	neutral	None	None	None	None	I
S/F	0.7789	likely_pathogenic	0.8185	pathogenic	-0.972	Destabilizing	0.991	D	0.688	prob.neutral	N	0.485830453	None	None	I
S/G	0.2557	likely_benign	0.2995	benign	-0.901	Destabilizing	0.953	D	0.485	neutral	None	None	None	None	I
S/H	0.8313	likely_pathogenic	0.8538	pathogenic	-1.332	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
S/I	0.6092	likely_pathogenic	0.6984	pathogenic	-0.287	Destabilizing	0.986	D	0.702	prob.neutral	None	None	None	None	I
S/K	0.9841	likely_pathogenic	0.988	pathogenic	-0.744	Destabilizing	0.953	D	0.537	neutral	None	None	None	None	I
S/L	0.3822	ambiguous	0.4786	ambiguous	-0.287	Destabilizing	0.91	D	0.544	neutral	None	None	None	None	I
S/M	0.4405	ambiguous	0.5122	ambiguous	-0.074	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
S/N	0.4808	ambiguous	0.5447	ambiguous	-0.585	Destabilizing	0.953	D	0.532	neutral	None	None	None	None	I
S/P	0.981	likely_pathogenic	0.9851	pathogenic	-0.393	Destabilizing	0.991	D	0.689	prob.neutral	N	0.482231338	None	None	I
S/Q	0.8682	likely_pathogenic	0.8873	pathogenic	-0.78	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	I
S/R	0.9783	likely_pathogenic	0.9829	pathogenic	-0.554	Destabilizing	0.986	D	0.692	prob.neutral	None	None	None	None	I
S/T	0.2008	likely_benign	0.2498	benign	-0.666	Destabilizing	0.17	N	0.28	neutral	N	0.471053001	None	None	I
S/V	0.5404	ambiguous	0.6283	pathogenic	-0.393	Destabilizing	0.973	D	0.609	neutral	None	None	None	None	I
S/W	0.8589	likely_pathogenic	0.8846	pathogenic	-0.921	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	I
S/Y	0.7095	likely_pathogenic	0.7537	pathogenic	-0.684	Destabilizing	0.997	D	0.687	prob.neutral	N	0.508803313	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.