TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33570	100933;100934;100935	chr2:178536039;178536038;178536037	chr2:179400766;179400765;179400764
N2AB	31929	96010;96011;96012	chr2:178536039;178536038;178536037	chr2:179400766;179400765;179400764
N2A	31002	93229;93230;93231	chr2:178536039;178536038;178536037	chr2:179400766;179400765;179400764
N2B	24505	73738;73739;73740	chr2:178536039;178536038;178536037	chr2:179400766;179400765;179400764
Novex-1	24630	74113;74114;74115	chr2:178536039;178536038;178536037	chr2:179400766;179400765;179400764
Novex-2	24697	74314;74315;74316	chr2:178536039;178536038;178536037	chr2:179400766;179400765;179400764
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-158
• Domain position: 75
• Structural Position: 156
• Q(SASA): 0.0794
• 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/F	rs1208247404	None	0.059	D	0.601	0.594	0.72348304321	gnomAD-4.0.0	1.66186E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.99045E-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	0.8884	likely_pathogenic	0.8669	pathogenic	-1.904	Destabilizing	0.915	D	0.698	prob.neutral	N	0.508528625	None	None	N
V/C	0.9375	likely_pathogenic	0.9392	pathogenic	-1.255	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9982	pathogenic	-2.732	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.558894893	None	None	N
V/E	0.9963	likely_pathogenic	0.9945	pathogenic	-2.452	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/F	0.8744	likely_pathogenic	0.858	pathogenic	-1.049	Destabilizing	0.059	N	0.601	neutral	D	0.541462902	None	None	N
V/G	0.9358	likely_pathogenic	0.8962	pathogenic	-2.488	Highly Destabilizing	0.996	D	0.866	deleterious	D	0.558693089	None	None	N
V/H	0.9991	likely_pathogenic	0.9987	pathogenic	-2.41	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.1096	likely_benign	0.1435	benign	-0.237	Destabilizing	0.054	N	0.356	neutral	N	0.487508974	None	None	N
V/K	0.9976	likely_pathogenic	0.9967	pathogenic	-1.426	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/L	0.6421	likely_pathogenic	0.6835	pathogenic	-0.237	Destabilizing	0.257	N	0.588	neutral	D	0.522274908	None	None	N
V/M	0.7227	likely_pathogenic	0.773	pathogenic	-0.347	Destabilizing	0.993	D	0.676	prob.neutral	None	None	None	None	N
V/N	0.9952	likely_pathogenic	0.9934	pathogenic	-1.94	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
V/P	0.9985	likely_pathogenic	0.9973	pathogenic	-0.769	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/Q	0.9955	likely_pathogenic	0.9933	pathogenic	-1.665	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/R	0.9956	likely_pathogenic	0.9929	pathogenic	-1.488	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/S	0.981	likely_pathogenic	0.9757	pathogenic	-2.502	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/T	0.9492	likely_pathogenic	0.9394	pathogenic	-2.07	Highly Destabilizing	0.997	D	0.737	prob.delet.	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.9984	pathogenic	-1.675	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/Y	0.992	likely_pathogenic	0.9895	pathogenic	-1.24	Destabilizing	0.999	D	0.795	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.