TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28941	87046;87047;87048	chr2:178559311;178558637;178558636	chr2:179424038;179423364;179423363
N2AB	27300	82123;82124;82125	chr2:178559311;178558637;178558636	chr2:179424038;179423364;179423363
N2A	26373	79342;79343;79344	chr2:178559311;178558637;178558636	chr2:179424038;179423364;179423363
N2B	19876	59851;59852;59853	chr2:178559311;178558637;178558636	chr2:179424038;179423364;179423363
Novex-1	20001	60226;60227;60228	chr2:178559311;178558637;178558636	chr2:179424038;179423364;179423363
Novex-2	20068	60427;60428;60429	chr2:178559311;178558637;178558636	chr2:179424038;179423364;179423363
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: Fn3-98
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.5855
• 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/D	rs1702394454	None	0.946	N	0.512	None	0.385743280973	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1702394454	None	0.946	N	0.512	None	0.385743280973	gnomAD-4.0.0	2.57384E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.79203E-06	0	0
E/K	None	None	0.996	N	0.646	0.355	0.440915056915	gnomAD-4.0.0	1.67668E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.99442E-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
E/A	0.4071	ambiguous	0.4043	ambiguous	-0.283	Destabilizing	0.993	D	0.7	prob.delet.	N	0.463346025	None	None	N
E/C	0.962	likely_pathogenic	0.9629	pathogenic	-0.052	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.4912	ambiguous	0.4627	ambiguous	-0.347	Destabilizing	0.946	D	0.512	neutral	N	0.45671548	None	None	N
E/F	0.9836	likely_pathogenic	0.984	pathogenic	-0.211	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/G	0.3825	ambiguous	0.3812	ambiguous	-0.459	Destabilizing	0.999	D	0.587	neutral	N	0.463817005	None	None	N
E/H	0.9118	likely_pathogenic	0.9094	pathogenic	0.108	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/I	0.9057	likely_pathogenic	0.9055	pathogenic	0.138	Stabilizing	0.998	D	0.722	deleterious	None	None	None	None	N
E/K	0.5195	ambiguous	0.5415	ambiguous	0.401	Stabilizing	0.996	D	0.646	neutral	N	0.488557532	None	None	N
E/L	0.8777	likely_pathogenic	0.8779	pathogenic	0.138	Stabilizing	0.998	D	0.659	prob.neutral	None	None	None	None	N
E/M	0.8232	likely_pathogenic	0.8161	pathogenic	0.146	Stabilizing	0.997	D	0.775	deleterious	None	None	None	None	N
E/N	0.7408	likely_pathogenic	0.7199	pathogenic	0.07	Stabilizing	0.996	D	0.766	deleterious	None	None	None	None	N
E/P	0.9928	likely_pathogenic	0.9929	pathogenic	0.018	Stabilizing	0.988	D	0.747	deleterious	None	None	None	None	N
E/Q	0.215	likely_benign	0.2235	benign	0.098	Stabilizing	0.998	D	0.612	neutral	N	0.513571627	None	None	N
E/R	0.6698	likely_pathogenic	0.6808	pathogenic	0.598	Stabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
E/S	0.5084	ambiguous	0.4974	ambiguous	-0.065	Destabilizing	0.994	D	0.701	prob.delet.	None	None	None	None	N
E/T	0.6718	likely_pathogenic	0.6625	pathogenic	0.081	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
E/V	0.6948	likely_pathogenic	0.6971	pathogenic	0.018	Stabilizing	0.997	D	0.673	prob.neutral	N	0.497520755	None	None	N
E/W	0.9931	likely_pathogenic	0.9937	pathogenic	-0.086	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Y	0.9674	likely_pathogenic	0.967	pathogenic	0.029	Stabilizing	1.0	D	0.734	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.