TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9902	29929;29930;29931	chr2:178704768;178704767;178704766	chr2:179569495;179569494;179569493
N2AB	9585	28978;28979;28980	chr2:178704768;178704767;178704766	chr2:179569495;179569494;179569493
N2A	8658	26197;26198;26199	chr2:178704768;178704767;178704766	chr2:179569495;179569494;179569493
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-84
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2813
• 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/R	rs1430193759	None	0.999	None	0.758	0.487	0.652799619513	gnomAD-4.0.0	1.60219E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86533E-06	0	0
L/V	None	None	0.198	None	0.365	0.119	0.285316908763	gnomAD-4.0.0	1.60252E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86599E-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
L/A	0.9254	likely_pathogenic	0.8438	pathogenic	-1.724	Destabilizing	0.983	D	0.62	neutral	None	None	None	None	I
L/C	0.9647	likely_pathogenic	0.934	pathogenic	-0.841	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
L/D	0.9977	likely_pathogenic	0.9916	pathogenic	-1.328	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
L/E	0.9799	likely_pathogenic	0.9419	pathogenic	-1.314	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	I
L/F	0.8172	likely_pathogenic	0.6324	pathogenic	-1.22	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	I
L/G	0.9927	likely_pathogenic	0.9782	pathogenic	-2.059	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	I
L/H	0.9602	likely_pathogenic	0.899	pathogenic	-1.293	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
L/I	0.2603	likely_benign	0.1922	benign	-0.867	Destabilizing	0.923	D	0.555	neutral	None	None	None	None	I
L/K	0.9237	likely_pathogenic	0.846	pathogenic	-1.254	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
L/M	0.4404	ambiguous	0.3267	benign	-0.584	Destabilizing	0.997	D	0.745	deleterious	None	None	None	None	I
L/N	0.9813	likely_pathogenic	0.9565	pathogenic	-1.03	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
L/P	0.9834	likely_pathogenic	0.9394	pathogenic	-1.123	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
L/Q	0.9269	likely_pathogenic	0.82	pathogenic	-1.192	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	I
L/R	0.9065	likely_pathogenic	0.7938	pathogenic	-0.643	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	I
L/S	0.9809	likely_pathogenic	0.9458	pathogenic	-1.585	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	I
L/T	0.9111	likely_pathogenic	0.8213	pathogenic	-1.457	Destabilizing	0.983	D	0.685	prob.neutral	None	None	None	None	I
L/V	0.2973	likely_benign	0.2083	benign	-1.123	Destabilizing	0.198	N	0.365	neutral	None	None	None	None	I
L/W	0.958	likely_pathogenic	0.8774	pathogenic	-1.334	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
L/Y	0.966	likely_pathogenic	0.9257	pathogenic	-1.12	Destabilizing	0.999	D	0.779	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.