TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29708	89347;89348;89349	chr2:178553989;178553988;178553987	chr2:179418716;179418715;179418714
N2AB	28067	84424;84425;84426	chr2:178553989;178553988;178553987	chr2:179418716;179418715;179418714
N2A	27140	81643;81644;81645	chr2:178553989;178553988;178553987	chr2:179418716;179418715;179418714
N2B	20643	62152;62153;62154	chr2:178553989;178553988;178553987	chr2:179418716;179418715;179418714
Novex-1	20768	62527;62528;62529	chr2:178553989;178553988;178553987	chr2:179418716;179418715;179418714
Novex-2	20835	62728;62729;62730	chr2:178553989;178553988;178553987	chr2:179418716;179418715;179418714
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-104
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0886
• 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/G	None	None	0.964	D	0.816	0.761	0.906977160548	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	2.77393E-05	None	0	0	0	0	0
V/L	None	None	0.863	D	0.597	0.587	0.815628326125	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
V/A	0.6299	likely_pathogenic	0.5459	ambiguous	-2.493	Highly Destabilizing	0.046	N	0.313	neutral	D	0.550175263	None	None	N
V/C	0.9371	likely_pathogenic	0.9304	pathogenic	-1.761	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9984	pathogenic	-3.2	Highly Destabilizing	0.991	D	0.881	deleterious	D	0.649914155	None	None	N
V/E	0.995	likely_pathogenic	0.9958	pathogenic	-2.882	Highly Destabilizing	0.986	D	0.833	deleterious	None	None	None	None	N
V/F	0.9566	likely_pathogenic	0.958	pathogenic	-1.231	Destabilizing	0.997	D	0.771	deleterious	D	0.582104586	None	None	N
V/G	0.8853	likely_pathogenic	0.891	pathogenic	-3.075	Highly Destabilizing	0.964	D	0.816	deleterious	D	0.649914155	None	None	N
V/H	0.9988	likely_pathogenic	0.9989	pathogenic	-2.829	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
V/I	0.1352	likely_benign	0.1323	benign	-0.779	Destabilizing	0.863	D	0.533	neutral	N	0.49279049	None	None	N
V/K	0.9975	likely_pathogenic	0.998	pathogenic	-1.744	Destabilizing	0.986	D	0.835	deleterious	None	None	None	None	N
V/L	0.8111	likely_pathogenic	0.7988	pathogenic	-0.779	Destabilizing	0.863	D	0.597	neutral	D	0.526533919	None	None	N
V/M	0.8783	likely_pathogenic	0.8744	pathogenic	-1.161	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
V/N	0.9903	likely_pathogenic	0.9919	pathogenic	-2.409	Highly Destabilizing	0.993	D	0.885	deleterious	None	None	None	None	N
V/P	0.9951	likely_pathogenic	0.995	pathogenic	-1.336	Destabilizing	0.993	D	0.851	deleterious	None	None	None	None	N
V/Q	0.9946	likely_pathogenic	0.9953	pathogenic	-2.037	Highly Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
V/R	0.9926	likely_pathogenic	0.9939	pathogenic	-1.893	Destabilizing	0.993	D	0.889	deleterious	None	None	None	None	N
V/S	0.92	likely_pathogenic	0.9079	pathogenic	-2.886	Highly Destabilizing	0.973	D	0.789	deleterious	None	None	None	None	N
V/T	0.8727	likely_pathogenic	0.8451	pathogenic	-2.419	Highly Destabilizing	0.953	D	0.622	neutral	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9996	pathogenic	-1.704	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/Y	0.9954	likely_pathogenic	0.996	pathogenic	-1.503	Destabilizing	0.998	D	0.777	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.