TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20735	62428;62429;62430	chr2:178589522;178589521;178589520	chr2:179454249;179454248;179454247
N2AB	19094	57505;57506;57507	chr2:178589522;178589521;178589520	chr2:179454249;179454248;179454247
N2A	18167	54724;54725;54726	chr2:178589522;178589521;178589520	chr2:179454249;179454248;179454247
N2B	11670	35233;35234;35235	chr2:178589522;178589521;178589520	chr2:179454249;179454248;179454247
Novex-1	11795	35608;35609;35610	chr2:178589522;178589521;178589520	chr2:179454249;179454248;179454247
Novex-2	11862	35809;35810;35811	chr2:178589522;178589521;178589520	chr2:179454249;179454248;179454247
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-38
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.3686
• 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
E/G	rs767027188	-1.191	1.0	N	0.584	0.558	0.469660041277	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
E/G	rs767027188	-1.191	1.0	N	0.584	0.558	0.469660041277	gnomAD-4.0.0	1.59219E-06	None	None	None	None	N	None	0	0	None	0	2.78334E-05	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
E/A	0.6723	likely_pathogenic	0.7593	pathogenic	-0.771	Destabilizing	0.999	D	0.633	neutral	N	0.477494396	None	None	N
E/C	0.9906	likely_pathogenic	0.9955	pathogenic	-0.357	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
E/D	0.7387	likely_pathogenic	0.7942	pathogenic	-0.982	Destabilizing	0.999	D	0.571	neutral	N	0.490259961	None	None	N
E/F	0.9948	likely_pathogenic	0.9967	pathogenic	-0.476	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
E/G	0.8082	likely_pathogenic	0.8628	pathogenic	-1.085	Destabilizing	1.0	D	0.584	neutral	N	0.502034341	None	None	N
E/H	0.9824	likely_pathogenic	0.9901	pathogenic	-0.712	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
E/I	0.9336	likely_pathogenic	0.9644	pathogenic	0.066	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/K	0.8602	likely_pathogenic	0.8944	pathogenic	-0.467	Destabilizing	0.999	D	0.666	neutral	N	0.482662638	None	None	N
E/L	0.9606	likely_pathogenic	0.975	pathogenic	0.066	Stabilizing	1.0	D	0.61	neutral	None	None	None	None	N
E/M	0.9518	likely_pathogenic	0.9722	pathogenic	0.445	Stabilizing	1.0	D	0.58	neutral	None	None	None	None	N
E/N	0.9237	likely_pathogenic	0.9461	pathogenic	-0.817	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
E/P	0.886	likely_pathogenic	0.9248	pathogenic	-0.192	Destabilizing	1.0	D	0.588	neutral	None	None	None	None	N
E/Q	0.645	likely_pathogenic	0.7141	pathogenic	-0.736	Destabilizing	1.0	D	0.643	neutral	N	0.468926476	None	None	N
E/R	0.9214	likely_pathogenic	0.9416	pathogenic	-0.244	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
E/S	0.8465	likely_pathogenic	0.8863	pathogenic	-1.083	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/T	0.8901	likely_pathogenic	0.9104	pathogenic	-0.834	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
E/V	0.8523	likely_pathogenic	0.9189	pathogenic	-0.192	Destabilizing	1.0	D	0.583	neutral	N	0.490259961	None	None	N
E/W	0.9982	likely_pathogenic	0.9989	pathogenic	-0.291	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
E/Y	0.991	likely_pathogenic	0.9951	pathogenic	-0.244	Destabilizing	1.0	D	0.585	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.