TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17729	53410;53411;53412	chr2:178607503;178607502;178607501	chr2:179472230;179472229;179472228
N2AB	16088	48487;48488;48489	chr2:178607503;178607502;178607501	chr2:179472230;179472229;179472228
N2A	15161	45706;45707;45708	chr2:178607503;178607502;178607501	chr2:179472230;179472229;179472228
N2B	8664	26215;26216;26217	chr2:178607503;178607502;178607501	chr2:179472230;179472229;179472228
Novex-1	8789	26590;26591;26592	chr2:178607503;178607502;178607501	chr2:179472230;179472229;179472228
Novex-2	8856	26791;26792;26793	chr2:178607503;178607502;178607501	chr2:179472230;179472229;179472228
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-113
• Domain position: 53
• Structural Position: 138
• Q(SASA): 0.0845
• 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
L/V	rs767559716	-1.485	0.198	N	0.387	0.381	0.510872562601	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/V	rs767559716	-1.485	0.198	N	0.387	0.381	0.510872562601	gnomAD-4.0.0	6.84397E-07	None	None	None	None	N	None	0	2.23664E-05	None	0	0	None	0	0	0	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	0.8999	likely_pathogenic	0.9052	pathogenic	-2.636	Highly Destabilizing	0.983	D	0.705	prob.neutral	None	None	None	None	N
L/C	0.8938	likely_pathogenic	0.8871	pathogenic	-1.851	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9997	pathogenic	-3.507	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
L/E	0.9966	likely_pathogenic	0.998	pathogenic	-3.195	Highly Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
L/F	0.7349	likely_pathogenic	0.6605	pathogenic	-1.703	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
L/G	0.9855	likely_pathogenic	0.9886	pathogenic	-3.196	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
L/H	0.9936	likely_pathogenic	0.9956	pathogenic	-2.998	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/I	0.2034	likely_benign	0.2088	benign	-0.937	Destabilizing	0.9	D	0.64	neutral	N	0.501757393	None	None	N
L/K	0.9928	likely_pathogenic	0.9957	pathogenic	-2.247	Highly Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
L/M	0.3129	likely_benign	0.2911	benign	-1.111	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
L/N	0.9958	likely_pathogenic	0.9976	pathogenic	-3.037	Highly Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
L/P	0.9971	likely_pathogenic	0.9983	pathogenic	-1.498	Destabilizing	0.999	D	0.833	deleterious	D	0.565695398	None	None	N
L/Q	0.9876	likely_pathogenic	0.9922	pathogenic	-2.647	Highly Destabilizing	0.999	D	0.798	deleterious	D	0.565695398	None	None	N
L/R	0.9875	likely_pathogenic	0.9914	pathogenic	-2.388	Highly Destabilizing	0.999	D	0.794	deleterious	D	0.565695398	None	None	N
L/S	0.995	likely_pathogenic	0.9966	pathogenic	-3.452	Highly Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
L/T	0.973	likely_pathogenic	0.9829	pathogenic	-2.982	Highly Destabilizing	0.983	D	0.715	prob.delet.	None	None	None	None	N
L/V	0.2298	likely_benign	0.2372	benign	-1.498	Destabilizing	0.198	N	0.387	neutral	N	0.516356156	None	None	N
L/W	0.9744	likely_pathogenic	0.9726	pathogenic	-2.054	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/Y	0.9658	likely_pathogenic	0.9626	pathogenic	-1.889	Destabilizing	0.999	D	0.705	prob.neutral	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.