TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1339	4240;4241;4242	chr2:178779067;178779066;178779065	chr2:179643794;179643793;179643792
N2AB	1339	4240;4241;4242	chr2:178779067;178779066;178779065	chr2:179643794;179643793;179643792
N2A	1339	4240;4241;4242	chr2:178779067;178779066;178779065	chr2:179643794;179643793;179643792
N2B	1293	4102;4103;4104	chr2:178779067;178779066;178779065	chr2:179643794;179643793;179643792
Novex-1	1293	4102;4103;4104	chr2:178779067;178779066;178779065	chr2:179643794;179643793;179643792
Novex-2	1293	4102;4103;4104	chr2:178779067;178779066;178779065	chr2:179643794;179643793;179643792
Novex-3	1339	4240;4241;4242	chr2:178779067;178779066;178779065	chr2:179643794;179643793;179643792

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-5
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2727
• 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
M/I	rs1561323191	None	0.012	N	0.126	0.235	0.434045841721	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
M/A	0.88	likely_pathogenic	0.8925	pathogenic	-2.666	Highly Destabilizing	0.373	N	0.395	neutral	None	None	None	None	I
M/C	0.9517	likely_pathogenic	0.9554	pathogenic	-1.525	Destabilizing	0.996	D	0.539	neutral	None	None	None	None	I
M/D	0.9948	likely_pathogenic	0.9952	pathogenic	-1.314	Destabilizing	0.984	D	0.615	neutral	None	None	None	None	I
M/E	0.943	likely_pathogenic	0.9494	pathogenic	-1.221	Destabilizing	0.953	D	0.583	neutral	None	None	None	None	I
M/F	0.6828	likely_pathogenic	0.7167	pathogenic	-1.387	Destabilizing	0.742	D	0.495	neutral	None	None	None	None	I
M/G	0.9698	likely_pathogenic	0.9738	pathogenic	-3.05	Highly Destabilizing	0.854	D	0.588	neutral	None	None	None	None	I
M/H	0.9641	likely_pathogenic	0.9718	pathogenic	-2.135	Highly Destabilizing	0.996	D	0.573	neutral	None	None	None	None	I
M/I	0.6592	likely_pathogenic	0.6961	pathogenic	-1.601	Destabilizing	0.012	N	0.126	neutral	N	0.399463836	None	None	I
M/K	0.8257	likely_pathogenic	0.8546	pathogenic	-1.217	Destabilizing	0.815	D	0.513	neutral	N	0.502714098	None	None	I
M/L	0.3756	ambiguous	0.4257	ambiguous	-1.601	Destabilizing	0.078	N	0.241	neutral	N	0.442104984	None	None	I
M/N	0.9618	likely_pathogenic	0.966	pathogenic	-1.118	Destabilizing	0.984	D	0.587	neutral	None	None	None	None	I
M/P	0.992	likely_pathogenic	0.993	pathogenic	-1.935	Destabilizing	0.984	D	0.595	neutral	None	None	None	None	I
M/Q	0.7966	likely_pathogenic	0.8208	pathogenic	-1.107	Destabilizing	0.984	D	0.497	neutral	None	None	None	None	I
M/R	0.8462	likely_pathogenic	0.8797	pathogenic	-0.834	Destabilizing	0.939	D	0.563	neutral	N	0.514895807	None	None	I
M/S	0.9352	likely_pathogenic	0.943	pathogenic	-1.786	Destabilizing	0.742	D	0.465	neutral	None	None	None	None	I
M/T	0.7631	likely_pathogenic	0.7952	pathogenic	-1.577	Destabilizing	0.684	D	0.467	neutral	N	0.486443687	None	None	I
M/V	0.2569	likely_benign	0.2886	benign	-1.935	Destabilizing	0.003	N	0.109	neutral	N	0.466329945	None	None	I
M/W	0.9411	likely_pathogenic	0.9529	pathogenic	-1.338	Destabilizing	0.996	D	0.545	neutral	None	None	None	None	I
M/Y	0.9295	likely_pathogenic	0.9417	pathogenic	-1.474	Destabilizing	0.953	D	0.562	neutral	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.