TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33706	101341;101342;101343	chr2:178535499;178535498;178535497	chr2:179400226;179400225;179400224
N2AB	32065	96418;96419;96420	chr2:178535499;178535498;178535497	chr2:179400226;179400225;179400224
N2A	31138	93637;93638;93639	chr2:178535499;178535498;178535497	chr2:179400226;179400225;179400224
N2B	24641	74146;74147;74148	chr2:178535499;178535498;178535497	chr2:179400226;179400225;179400224
Novex-1	24766	74521;74522;74523	chr2:178535499;178535498;178535497	chr2:179400226;179400225;179400224
Novex-2	24833	74722;74723;74724	chr2:178535499;178535498;178535497	chr2:179400226;179400225;179400224
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: Fn3-132
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1126
• 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	rs1261733710	-2.657	0.005	N	0.374	0.141	0.316494231283	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/A	rs1261733710	-2.657	0.005	N	0.374	0.141	0.316494231283	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
V/L	None	None	0.107	N	0.523	0.09	0.278968121808	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	0.5748	likely_pathogenic	0.5299	ambiguous	-2.315	Highly Destabilizing	0.005	N	0.374	neutral	N	0.499415825	None	None	N
V/C	0.8518	likely_pathogenic	0.8595	pathogenic	-2.68	Highly Destabilizing	0.981	D	0.785	deleterious	None	None	None	None	N
V/D	0.9976	likely_pathogenic	0.9973	pathogenic	-2.987	Highly Destabilizing	0.997	D	0.875	deleterious	D	0.528967368	None	None	N
V/E	0.991	likely_pathogenic	0.9894	pathogenic	-2.761	Highly Destabilizing	0.988	D	0.867	deleterious	None	None	None	None	N
V/F	0.8671	likely_pathogenic	0.8068	pathogenic	-1.62	Destabilizing	0.98	D	0.846	deleterious	N	0.514911583	None	None	N
V/G	0.893	likely_pathogenic	0.8747	pathogenic	-2.84	Highly Destabilizing	0.894	D	0.841	deleterious	N	0.505076215	None	None	N
V/H	0.9971	likely_pathogenic	0.9971	pathogenic	-2.54	Highly Destabilizing	0.995	D	0.843	deleterious	None	None	None	None	N
V/I	0.1232	likely_benign	0.1171	benign	-0.836	Destabilizing	None	N	0.241	neutral	N	0.458875925	None	None	N
V/K	0.9923	likely_pathogenic	0.9918	pathogenic	-1.961	Destabilizing	0.994	D	0.866	deleterious	None	None	None	None	N
V/L	0.5112	ambiguous	0.4548	ambiguous	-0.836	Destabilizing	0.107	N	0.523	neutral	N	0.495292511	None	None	N
V/M	0.5758	likely_pathogenic	0.4754	ambiguous	-1.304	Destabilizing	0.979	D	0.698	prob.neutral	None	None	None	None	N
V/N	0.9887	likely_pathogenic	0.9887	pathogenic	-2.415	Highly Destabilizing	0.982	D	0.871	deleterious	None	None	None	None	N
V/P	0.9973	likely_pathogenic	0.9978	pathogenic	-1.305	Destabilizing	0.982	D	0.849	deleterious	None	None	None	None	N
V/Q	0.9856	likely_pathogenic	0.9844	pathogenic	-2.258	Highly Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	N
V/R	0.9843	likely_pathogenic	0.9835	pathogenic	-1.802	Destabilizing	0.997	D	0.868	deleterious	None	None	None	None	N
V/S	0.9177	likely_pathogenic	0.913	pathogenic	-3.083	Highly Destabilizing	0.771	D	0.848	deleterious	None	None	None	None	N
V/T	0.7953	likely_pathogenic	0.774	pathogenic	-2.699	Highly Destabilizing	0.279	N	0.709	prob.delet.	None	None	None	None	N
V/W	0.998	likely_pathogenic	0.9975	pathogenic	-2.006	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
V/Y	0.9904	likely_pathogenic	0.9873	pathogenic	-1.677	Destabilizing	0.987	D	0.812	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.