TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27785	83578;83579;83580	chr2:178562779;178562778;178562777	chr2:179427506;179427505;179427504
N2AB	26144	78655;78656;78657	chr2:178562779;178562778;178562777	chr2:179427506;179427505;179427504
N2A	25217	75874;75875;75876	chr2:178562779;178562778;178562777	chr2:179427506;179427505;179427504
N2B	18720	56383;56384;56385	chr2:178562779;178562778;178562777	chr2:179427506;179427505;179427504
Novex-1	18845	56758;56759;56760	chr2:178562779;178562778;178562777	chr2:179427506;179427505;179427504
Novex-2	18912	56959;56960;56961	chr2:178562779;178562778;178562777	chr2:179427506;179427505;179427504
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-90
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.081
• 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/F	None	None	0.994	D	0.689	0.374	0.641816012551	gnomAD-4.0.0	1.59239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43332E-05	0
L/S	None	None	1.0	D	0.879	0.628	0.808818361352	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8485	likely_pathogenic	0.8659	pathogenic	-2.527	Highly Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
L/C	0.8359	likely_pathogenic	0.8597	pathogenic	-1.516	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9996	pathogenic	-2.976	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/E	0.9968	likely_pathogenic	0.9973	pathogenic	-2.631	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/F	0.4699	ambiguous	0.5468	ambiguous	-1.527	Destabilizing	0.994	D	0.689	prob.neutral	D	0.539814511	None	None	N
L/G	0.9879	likely_pathogenic	0.9895	pathogenic	-3.151	Highly Destabilizing	0.999	D	0.911	deleterious	None	None	None	None	N
L/H	0.9901	likely_pathogenic	0.9923	pathogenic	-3.049	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/I	0.0723	likely_benign	0.079	benign	-0.636	Destabilizing	0.034	N	0.333	neutral	None	None	None	None	N
L/K	0.9942	likely_pathogenic	0.9957	pathogenic	-1.743	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/M	0.24	likely_benign	0.2601	benign	-0.836	Destabilizing	0.979	D	0.667	neutral	N	0.515304701	None	None	N
L/N	0.9966	likely_pathogenic	0.9971	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/P	0.9935	likely_pathogenic	0.9951	pathogenic	-1.26	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
L/Q	0.9873	likely_pathogenic	0.9899	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/R	0.9879	likely_pathogenic	0.9912	pathogenic	-2.098	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
L/S	0.9863	likely_pathogenic	0.9883	pathogenic	-3.019	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.552438264	None	None	N
L/T	0.9354	likely_pathogenic	0.937	pathogenic	-2.493	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/V	0.0927	likely_benign	0.0976	benign	-1.26	Destabilizing	0.132	N	0.35	neutral	D	0.524122269	None	None	N
L/W	0.9626	likely_pathogenic	0.9757	pathogenic	-1.827	Destabilizing	1.0	D	0.857	deleterious	D	0.563794569	None	None	N
L/Y	0.9509	likely_pathogenic	0.9655	pathogenic	-1.669	Destabilizing	0.999	D	0.787	deleterious	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.