TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7818	23677;23678;23679	chr2:178720190;178720189;178720188	chr2:179584917;179584916;179584915
N2AB	7501	22726;22727;22728	chr2:178720190;178720189;178720188	chr2:179584917;179584916;179584915
N2A	6574	19945;19946;19947	chr2:178720190;178720189;178720188	chr2:179584917;179584916;179584915
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-63
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0943
• 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/A	None	None	0.76	D	0.643	0.512	0.699956752411	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85871E-06	0	0
V/M	rs748019401	-0.43	0.997	D	0.747	0.514	0.681819901562	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/M	rs748019401	-0.43	0.997	D	0.747	0.514	0.681819901562	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85871E-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	0.4745	ambiguous	0.4318	ambiguous	-1.93	Destabilizing	0.76	D	0.643	neutral	D	0.532067827	None	None	N
V/C	0.9379	likely_pathogenic	0.9236	pathogenic	-1.241	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/D	0.9944	likely_pathogenic	0.9936	pathogenic	-2.818	Highly Destabilizing	0.986	D	0.855	deleterious	None	None	None	None	N
V/E	0.9801	likely_pathogenic	0.9759	pathogenic	-2.521	Highly Destabilizing	0.982	D	0.836	deleterious	D	0.606892255	None	None	N
V/F	0.6686	likely_pathogenic	0.6298	pathogenic	-1.082	Destabilizing	0.993	D	0.833	deleterious	None	None	None	None	N
V/G	0.8367	likely_pathogenic	0.8051	pathogenic	-2.525	Highly Destabilizing	0.982	D	0.838	deleterious	D	0.597373505	None	None	N
V/H	0.9937	likely_pathogenic	0.9923	pathogenic	-2.482	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
V/I	0.1019	likely_benign	0.0932	benign	-0.222	Destabilizing	0.893	D	0.572	neutral	None	None	None	None	N
V/K	0.9876	likely_pathogenic	0.985	pathogenic	-1.49	Destabilizing	0.986	D	0.839	deleterious	None	None	None	None	N
V/L	0.4862	ambiguous	0.4388	ambiguous	-0.222	Destabilizing	0.76	D	0.639	neutral	D	0.577471854	None	None	N
V/M	0.4876	ambiguous	0.4045	ambiguous	-0.343	Destabilizing	0.997	D	0.747	deleterious	D	0.590469286	None	None	N
V/N	0.9831	likely_pathogenic	0.9789	pathogenic	-2.073	Highly Destabilizing	0.986	D	0.847	deleterious	None	None	None	None	N
V/P	0.9671	likely_pathogenic	0.9695	pathogenic	-0.769	Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9762	likely_pathogenic	0.9705	pathogenic	-1.76	Destabilizing	0.993	D	0.848	deleterious	None	None	None	None	N
V/R	0.9755	likely_pathogenic	0.9717	pathogenic	-1.594	Destabilizing	0.993	D	0.849	deleterious	None	None	None	None	N
V/S	0.8576	likely_pathogenic	0.8208	pathogenic	-2.611	Highly Destabilizing	0.973	D	0.805	deleterious	None	None	None	None	N
V/T	0.5405	ambiguous	0.499	ambiguous	-2.158	Highly Destabilizing	0.214	N	0.328	neutral	None	None	None	None	N
V/W	0.992	likely_pathogenic	0.9901	pathogenic	-1.715	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/Y	0.9773	likely_pathogenic	0.9736	pathogenic	-1.276	Destabilizing	0.998	D	0.829	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.