TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29243	87952;87953;87954	chr2:178557535;178557534;178557533	chr2:179422262;179422261;179422260
N2AB	27602	83029;83030;83031	chr2:178557535;178557534;178557533	chr2:179422262;179422261;179422260
N2A	26675	80248;80249;80250	chr2:178557535;178557534;178557533	chr2:179422262;179422261;179422260
N2B	20178	60757;60758;60759	chr2:178557535;178557534;178557533	chr2:179422262;179422261;179422260
Novex-1	20303	61132;61133;61134	chr2:178557535;178557534;178557533	chr2:179422262;179422261;179422260
Novex-2	20370	61333;61334;61335	chr2:178557535;178557534;178557533	chr2:179422262;179422261;179422260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-101
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.3304
• 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
T/I	rs1559256317	None	0.925	N	0.515	0.254	0.357519025918	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
T/I	rs1559256317	None	0.925	N	0.515	0.254	0.357519025918	gnomAD-4.0.0	3.18227E-06	None	None	None	None	N	None	0	4.57268E-05	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
T/A	0.1125	likely_benign	0.1355	benign	-0.939	Destabilizing	0.248	N	0.152	neutral	N	0.483366151	None	None	N
T/C	0.5739	likely_pathogenic	0.682	pathogenic	-0.542	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	N
T/D	0.7505	likely_pathogenic	0.837	pathogenic	-0.465	Destabilizing	0.991	D	0.519	neutral	None	None	None	None	N
T/E	0.5611	ambiguous	0.6544	pathogenic	-0.465	Destabilizing	0.942	D	0.521	neutral	None	None	None	None	N
T/F	0.463	ambiguous	0.5761	pathogenic	-1.012	Destabilizing	0.996	D	0.668	neutral	None	None	None	None	N
T/G	0.5647	likely_pathogenic	0.6404	pathogenic	-1.199	Destabilizing	0.97	D	0.592	neutral	None	None	None	None	N
T/H	0.4307	ambiguous	0.5567	ambiguous	-1.496	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
T/I	0.2286	likely_benign	0.2758	benign	-0.333	Destabilizing	0.925	D	0.515	neutral	N	0.498335603	None	None	N
T/K	0.2804	likely_benign	0.3441	ambiguous	-0.884	Destabilizing	0.925	D	0.509	neutral	N	0.472399795	None	None	N
T/L	0.1464	likely_benign	0.1875	benign	-0.333	Destabilizing	0.942	D	0.501	neutral	None	None	None	None	N
T/M	0.1082	likely_benign	0.1354	benign	0.045	Stabilizing	0.996	D	0.584	neutral	None	None	None	None	N
T/N	0.2694	likely_benign	0.3312	benign	-0.829	Destabilizing	0.996	D	0.478	neutral	None	None	None	None	N
T/P	0.161	likely_benign	0.1967	benign	-0.503	Destabilizing	0.998	D	0.591	neutral	N	0.467802052	None	None	N
T/Q	0.3028	likely_benign	0.3723	ambiguous	-1.01	Destabilizing	0.746	D	0.35	neutral	None	None	None	None	N
T/R	0.2546	likely_benign	0.3437	ambiguous	-0.619	Destabilizing	0.989	D	0.579	neutral	N	0.503472064	None	None	N
T/S	0.2033	likely_benign	0.245	benign	-1.084	Destabilizing	0.925	D	0.467	neutral	N	0.47580546	None	None	N
T/V	0.1631	likely_benign	0.191	benign	-0.503	Destabilizing	0.304	N	0.198	neutral	None	None	None	None	N
T/W	0.8295	likely_pathogenic	0.9017	pathogenic	-0.938	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/Y	0.5095	ambiguous	0.6193	pathogenic	-0.722	Destabilizing	0.999	D	0.667	neutral	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.