TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1925	5998;5999;6000	chr2:178776091;178776090;178776089	chr2:179640818;179640817;179640816
N2AB	1925	5998;5999;6000	chr2:178776091;178776090;178776089	chr2:179640818;179640817;179640816
N2A	1925	5998;5999;6000	chr2:178776091;178776090;178776089	chr2:179640818;179640817;179640816
N2B	1879	5860;5861;5862	chr2:178776091;178776090;178776089	chr2:179640818;179640817;179640816
Novex-1	1879	5860;5861;5862	chr2:178776091;178776090;178776089	chr2:179640818;179640817;179640816
Novex-2	1879	5860;5861;5862	chr2:178776091;178776090;178776089	chr2:179640818;179640817;179640816
Novex-3	1925	5998;5999;6000	chr2:178776091;178776090;178776089	chr2:179640818;179640817;179640816

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-9
• Domain position: 85
• Structural Position: 172
• Q(SASA): 0.0714
• 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	0.999	N	0.635	0.461	0.536521311054	gnomAD-4.0.0	3.18102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71314E-06	0	0
V/M	None	None	1.0	D	0.759	0.503	0.616271755186	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	0.5769	likely_pathogenic	0.6078	pathogenic	-2.16	Highly Destabilizing	0.999	D	0.635	neutral	N	0.46457887	None	None	N
V/C	0.8808	likely_pathogenic	0.8749	pathogenic	-1.435	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/D	0.981	likely_pathogenic	0.9846	pathogenic	-2.909	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/E	0.9434	likely_pathogenic	0.9489	pathogenic	-2.736	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.636232009	None	None	N
V/F	0.8124	likely_pathogenic	0.7822	pathogenic	-1.362	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/G	0.7025	likely_pathogenic	0.7475	pathogenic	-2.635	Highly Destabilizing	1.0	D	0.886	deleterious	N	0.501614064	None	None	N
V/H	0.9884	likely_pathogenic	0.9884	pathogenic	-2.423	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
V/I	0.1774	likely_benign	0.162	benign	-0.844	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
V/K	0.9742	likely_pathogenic	0.9765	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/L	0.7431	likely_pathogenic	0.7491	pathogenic	-0.844	Destabilizing	0.997	D	0.641	neutral	D	0.549973804	None	None	N
V/M	0.6373	likely_pathogenic	0.6317	pathogenic	-0.639	Destabilizing	1.0	D	0.759	deleterious	D	0.569178212	None	None	N
V/N	0.9401	likely_pathogenic	0.943	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
V/P	0.9955	likely_pathogenic	0.9966	pathogenic	-1.257	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/Q	0.9457	likely_pathogenic	0.9465	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/R	0.9651	likely_pathogenic	0.9675	pathogenic	-1.662	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
V/S	0.7875	likely_pathogenic	0.8014	pathogenic	-2.659	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
V/T	0.5529	ambiguous	0.5658	pathogenic	-2.372	Highly Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
V/W	0.9964	likely_pathogenic	0.9959	pathogenic	-1.916	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/Y	0.9782	likely_pathogenic	0.9747	pathogenic	-1.559	Destabilizing	1.0	D	0.894	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.