TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22428	67507;67508;67509	chr2:178580005;178580004;178580003	chr2:179444732;179444731;179444730
N2AB	20787	62584;62585;62586	chr2:178580005;178580004;178580003	chr2:179444732;179444731;179444730
N2A	19860	59803;59804;59805	chr2:178580005;178580004;178580003	chr2:179444732;179444731;179444730
N2B	13363	40312;40313;40314	chr2:178580005;178580004;178580003	chr2:179444732;179444731;179444730
Novex-1	13488	40687;40688;40689	chr2:178580005;178580004;178580003	chr2:179444732;179444731;179444730
Novex-2	13555	40888;40889;40890	chr2:178580005;178580004;178580003	chr2:179444732;179444731;179444730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-50
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0911
• 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
V/L	rs794729483	-0.87	0.034	D	0.547	0.371	0.489104616352	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
V/L	rs794729483	-0.87	0.034	D	0.547	0.371	0.489104616352	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs794729483	-0.87	0.034	D	0.547	0.371	0.489104616352	gnomAD-4.0.0	8.67838E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18692E-05	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
V/A	0.9351	likely_pathogenic	0.9246	pathogenic	-2.591	Highly Destabilizing	0.007	N	0.335	neutral	D	0.569760776	None	None	N
V/C	0.9695	likely_pathogenic	0.9558	pathogenic	-1.736	Destabilizing	0.982	D	0.755	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9987	pathogenic	-3.395	Highly Destabilizing	0.826	D	0.894	deleterious	None	None	None	None	N
V/E	0.995	likely_pathogenic	0.9968	pathogenic	-3.091	Highly Destabilizing	0.781	D	0.843	deleterious	D	0.658039918	None	None	N
V/F	0.955	likely_pathogenic	0.9418	pathogenic	-1.534	Destabilizing	0.7	D	0.743	deleterious	None	None	None	None	N
V/G	0.9437	likely_pathogenic	0.9557	pathogenic	-3.133	Highly Destabilizing	0.638	D	0.829	deleterious	D	0.658039918	None	None	N
V/H	0.999	likely_pathogenic	0.9991	pathogenic	-2.907	Highly Destabilizing	0.982	D	0.883	deleterious	None	None	None	None	N
V/I	0.132	likely_benign	0.1096	benign	-0.981	Destabilizing	0.002	N	0.282	neutral	None	None	None	None	N
V/K	0.9965	likely_pathogenic	0.9976	pathogenic	-2.103	Highly Destabilizing	0.826	D	0.849	deleterious	None	None	None	None	N
V/L	0.8745	likely_pathogenic	0.8228	pathogenic	-0.981	Destabilizing	0.034	N	0.547	neutral	D	0.536244383	None	None	N
V/M	0.9337	likely_pathogenic	0.9054	pathogenic	-1.196	Destabilizing	0.638	D	0.667	neutral	D	0.55865796	None	None	N
V/N	0.9921	likely_pathogenic	0.994	pathogenic	-2.802	Highly Destabilizing	0.935	D	0.907	deleterious	None	None	None	None	N
V/P	0.9963	likely_pathogenic	0.9965	pathogenic	-1.506	Destabilizing	0.826	D	0.863	deleterious	None	None	None	None	N
V/Q	0.9954	likely_pathogenic	0.9966	pathogenic	-2.453	Highly Destabilizing	0.935	D	0.891	deleterious	None	None	None	None	N
V/R	0.9914	likely_pathogenic	0.9943	pathogenic	-2.167	Highly Destabilizing	0.826	D	0.904	deleterious	None	None	None	None	N
V/S	0.9755	likely_pathogenic	0.9785	pathogenic	-3.204	Highly Destabilizing	0.539	D	0.8	deleterious	None	None	None	None	N
V/T	0.9503	likely_pathogenic	0.9506	pathogenic	-2.762	Highly Destabilizing	0.399	N	0.602	neutral	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9993	pathogenic	-1.971	Destabilizing	0.982	D	0.85	deleterious	None	None	None	None	N
V/Y	0.9946	likely_pathogenic	0.9944	pathogenic	-1.784	Destabilizing	0.826	D	0.747	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.