TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32857	98794;98795;98796	chr2:178539496;178539495;178539494	chr2:179404223;179404222;179404221
N2AB	31216	93871;93872;93873	chr2:178539496;178539495;178539494	chr2:179404223;179404222;179404221
N2A	30289	91090;91091;91092	chr2:178539496;178539495;178539494	chr2:179404223;179404222;179404221
N2B	23792	71599;71600;71601	chr2:178539496;178539495;178539494	chr2:179404223;179404222;179404221
Novex-1	23917	71974;71975;71976	chr2:178539496;178539495;178539494	chr2:179404223;179404222;179404221
Novex-2	23984	72175;72176;72177	chr2:178539496;178539495;178539494	chr2:179404223;179404222;179404221
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-127
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1146
• 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/I	rs1472412628	0.185	0.997	N	0.548	0.233	0.555827534791	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs1472412628	0.185	0.997	N	0.548	0.233	0.555827534791	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	5.65483E-05	0	None	0	0	None	0	0	0	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	0.7076	likely_pathogenic	0.5797	pathogenic	-1.667	Destabilizing	0.999	D	0.653	neutral	D	0.527202646	None	None	N
V/C	0.935	likely_pathogenic	0.9079	pathogenic	-1.265	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/D	0.9938	likely_pathogenic	0.9902	pathogenic	-1.955	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/E	0.9753	likely_pathogenic	0.9634	pathogenic	-1.695	Destabilizing	1.0	D	0.801	deleterious	D	0.535047435	None	None	N
V/F	0.769	likely_pathogenic	0.6486	pathogenic	-0.941	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
V/G	0.8811	likely_pathogenic	0.8268	pathogenic	-2.225	Highly Destabilizing	1.0	D	0.818	deleterious	D	0.535047435	None	None	N
V/H	0.9929	likely_pathogenic	0.9885	pathogenic	-1.962	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
V/I	0.1279	likely_benign	0.1183	benign	-0.103	Destabilizing	0.997	D	0.548	neutral	N	0.480907422	None	None	N
V/K	0.9838	likely_pathogenic	0.9768	pathogenic	-1.365	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/L	0.6291	likely_pathogenic	0.4946	ambiguous	-0.103	Destabilizing	0.997	D	0.661	neutral	N	0.52107639	None	None	N
V/M	0.684	likely_pathogenic	0.5518	ambiguous	-0.246	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
V/N	0.9825	likely_pathogenic	0.974	pathogenic	-1.818	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/P	0.9797	likely_pathogenic	0.9674	pathogenic	-0.597	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/Q	0.9699	likely_pathogenic	0.9551	pathogenic	-1.533	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/R	0.9721	likely_pathogenic	0.96	pathogenic	-1.452	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/S	0.9171	likely_pathogenic	0.8785	pathogenic	-2.466	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/T	0.854	likely_pathogenic	0.786	pathogenic	-2.031	Highly Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
V/W	0.9944	likely_pathogenic	0.9899	pathogenic	-1.393	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9758	likely_pathogenic	0.9592	pathogenic	-0.96	Destabilizing	1.0	D	0.773	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.