TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18916	56971;56972;56973	chr2:178598964;178598963;178598962	chr2:179463691;179463690;179463689
N2AB	17275	52048;52049;52050	chr2:178598964;178598963;178598962	chr2:179463691;179463690;179463689
N2A	16348	49267;49268;49269	chr2:178598964;178598963;178598962	chr2:179463691;179463690;179463689
N2B	9851	29776;29777;29778	chr2:178598964;178598963;178598962	chr2:179463691;179463690;179463689
Novex-1	9976	30151;30152;30153	chr2:178598964;178598963;178598962	chr2:179463691;179463690;179463689
Novex-2	10043	30352;30353;30354	chr2:178598964;178598963;178598962	chr2:179463691;179463690;179463689
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: Fn3-25
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2362
• Predicted PPI site: I

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/E	rs1296926879	-2.344	0.997	N	0.881	0.578	None	gnomAD-2.1.1	1.44E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.38E-05	1.42288E-04
V/E	rs1296926879	-2.344	0.997	N	0.881	0.578	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/E	rs1296926879	-2.344	0.997	N	0.881	0.578	None	gnomAD-4.0.0	9.30197E-06	None	None	None	None	I	None	0	1.66967E-05	None	0	0	None	0	0	8.47851E-06	2.1978E-05	3.20431E-05

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	0.9423	likely_pathogenic	0.9308	pathogenic	-1.924	Destabilizing	0.939	D	0.599	neutral	N	0.495223939	None	None	I
V/C	0.9824	likely_pathogenic	0.9762	pathogenic	-1.474	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
V/D	0.9973	likely_pathogenic	0.9962	pathogenic	-2.292	Highly Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	I
V/E	0.9893	likely_pathogenic	0.9869	pathogenic	-2.23	Highly Destabilizing	0.997	D	0.881	deleterious	N	0.508012276	None	None	I
V/F	0.9509	likely_pathogenic	0.9257	pathogenic	-1.41	Destabilizing	0.986	D	0.873	deleterious	None	None	None	None	I
V/G	0.9801	likely_pathogenic	0.9713	pathogenic	-2.313	Highly Destabilizing	0.997	D	0.876	deleterious	N	0.519115092	None	None	I
V/H	0.9982	likely_pathogenic	0.9974	pathogenic	-1.882	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	I
V/I	0.0748	likely_benign	0.0817	benign	-0.913	Destabilizing	0.06	N	0.28	neutral	None	None	None	None	I
V/K	0.9919	likely_pathogenic	0.9899	pathogenic	-1.642	Destabilizing	0.993	D	0.883	deleterious	None	None	None	None	I
V/L	0.6641	likely_pathogenic	0.6079	pathogenic	-0.913	Destabilizing	0.76	D	0.532	neutral	N	0.476133534	None	None	I
V/M	0.7908	likely_pathogenic	0.7399	pathogenic	-0.764	Destabilizing	0.982	D	0.791	deleterious	N	0.500250368	None	None	I
V/N	0.9892	likely_pathogenic	0.985	pathogenic	-1.606	Destabilizing	0.998	D	0.898	deleterious	None	None	None	None	I
V/P	0.9312	likely_pathogenic	0.9427	pathogenic	-1.218	Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	I
V/Q	0.9916	likely_pathogenic	0.988	pathogenic	-1.725	Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	I
V/R	0.9883	likely_pathogenic	0.9849	pathogenic	-1.137	Destabilizing	0.998	D	0.899	deleterious	None	None	None	None	I
V/S	0.9804	likely_pathogenic	0.9741	pathogenic	-2.146	Highly Destabilizing	0.993	D	0.873	deleterious	None	None	None	None	I
V/T	0.9422	likely_pathogenic	0.9247	pathogenic	-1.97	Destabilizing	0.953	D	0.739	prob.delet.	None	None	None	None	I
V/W	0.9991	likely_pathogenic	0.9987	pathogenic	-1.713	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	I
V/Y	0.9956	likely_pathogenic	0.9926	pathogenic	-1.412	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	I

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.