TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30890	92893;92894;92895	chr2:178548958;178548957;178548956	chr2:179413685;179413684;179413683
N2AB	29249	87970;87971;87972	chr2:178548958;178548957;178548956	chr2:179413685;179413684;179413683
N2A	28322	85189;85190;85191	chr2:178548958;178548957;178548956	chr2:179413685;179413684;179413683
N2B	21825	65698;65699;65700	chr2:178548958;178548957;178548956	chr2:179413685;179413684;179413683
Novex-1	21950	66073;66074;66075	chr2:178548958;178548957;178548956	chr2:179413685;179413684;179413683
Novex-2	22017	66274;66275;66276	chr2:178548958;178548957;178548956	chr2:179413685;179413684;179413683
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: Fn3-113
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.2489
• 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	None	None	0.565	N	0.459	0.217	0.320256813643	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
E/K	None	None	0.565	N	0.435	0.196	0.267755039894	gnomAD-4.0.0	1.59108E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85794E-06	0	0
E/V	None	None	0.82	N	0.453	0.282	0.387202362727	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1571	likely_benign	0.1463	benign	-0.791	Destabilizing	0.008	N	0.225	neutral	N	0.41754659	None	None	N
E/C	0.7795	likely_pathogenic	0.7667	pathogenic	-0.516	Destabilizing	0.989	D	0.629	neutral	None	None	None	None	N
E/D	0.1732	likely_benign	0.1703	benign	-1.075	Destabilizing	0.722	D	0.429	neutral	N	0.492103064	None	None	N
E/F	0.7808	likely_pathogenic	0.7651	pathogenic	-0.157	Destabilizing	0.961	D	0.61	neutral	None	None	None	None	N
E/G	0.2028	likely_benign	0.188	benign	-1.15	Destabilizing	0.565	D	0.459	neutral	N	0.490833628	None	None	N
E/H	0.5019	ambiguous	0.4631	ambiguous	-0.378	Destabilizing	0.961	D	0.439	neutral	None	None	None	None	N
E/I	0.4122	ambiguous	0.3735	ambiguous	0.187	Stabilizing	0.923	D	0.599	neutral	None	None	None	None	N
E/K	0.1818	likely_benign	0.1515	benign	-0.677	Destabilizing	0.565	D	0.435	neutral	N	0.457219699	None	None	N
E/L	0.4408	ambiguous	0.3964	ambiguous	0.187	Stabilizing	0.858	D	0.524	neutral	None	None	None	None	N
E/M	0.431	ambiguous	0.4041	ambiguous	0.524	Stabilizing	0.989	D	0.544	neutral	None	None	None	None	N
E/N	0.2879	likely_benign	0.2566	benign	-1.112	Destabilizing	0.923	D	0.448	neutral	None	None	None	None	N
E/P	0.9437	likely_pathogenic	0.9425	pathogenic	-0.118	Destabilizing	0.961	D	0.439	neutral	None	None	None	None	N
E/Q	0.1421	likely_benign	0.1255	benign	-0.976	Destabilizing	0.034	N	0.17	neutral	N	0.4189521	None	None	N
E/R	0.3057	likely_benign	0.2658	benign	-0.32	Destabilizing	0.858	D	0.442	neutral	None	None	None	None	N
E/S	0.2103	likely_benign	0.1878	benign	-1.409	Destabilizing	0.633	D	0.411	neutral	None	None	None	None	N
E/T	0.2348	likely_benign	0.2026	benign	-1.117	Destabilizing	0.775	D	0.393	neutral	None	None	None	None	N
E/V	0.232	likely_benign	0.2117	benign	-0.118	Destabilizing	0.82	D	0.453	neutral	N	0.419586818	None	None	N
E/W	0.9139	likely_pathogenic	0.9064	pathogenic	0.103	Stabilizing	0.996	D	0.62	neutral	None	None	None	None	N
E/Y	0.6664	likely_pathogenic	0.6351	pathogenic	0.084	Stabilizing	0.961	D	0.543	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.