TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32192	96799;96800;96801	chr2:178543399;178543398;178543397	chr2:179408126;179408125;179408124
N2AB	30551	91876;91877;91878	chr2:178543399;178543398;178543397	chr2:179408126;179408125;179408124
N2A	29624	89095;89096;89097	chr2:178543399;178543398;178543397	chr2:179408126;179408125;179408124
N2B	23127	69604;69605;69606	chr2:178543399;178543398;178543397	chr2:179408126;179408125;179408124
Novex-1	23252	69979;69980;69981	chr2:178543399;178543398;178543397	chr2:179408126;179408125;179408124
Novex-2	23319	70180;70181;70182	chr2:178543399;178543398;178543397	chr2:179408126;179408125;179408124
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-122
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.3714
• 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
E/A	None	None	0.99	N	0.79	0.455	0.402614778071	gnomAD-4.0.0	1.5912E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85806E-06	0	0
E/K	rs1286172719	None	0.995	N	0.799	0.354	0.432604763906	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs1286172719	None	0.995	N	0.799	0.354	0.432604763906	gnomAD-4.0.0	6.57056E-06	None	None	None	None	N	None	0	6.5505E-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
E/A	0.5081	ambiguous	0.4815	ambiguous	-0.627	Destabilizing	0.99	D	0.79	deleterious	N	0.473162302	None	None	N
E/C	0.9535	likely_pathogenic	0.9513	pathogenic	-0.244	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
E/D	0.4781	ambiguous	0.4453	ambiguous	-1.061	Destabilizing	0.928	D	0.741	deleterious	N	0.470617862	None	None	N
E/F	0.9431	likely_pathogenic	0.9381	pathogenic	0.305	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/G	0.6749	likely_pathogenic	0.6408	pathogenic	-1.076	Destabilizing	0.999	D	0.739	deleterious	N	0.482520826	None	None	N
E/H	0.8737	likely_pathogenic	0.8568	pathogenic	0.111	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/I	0.7116	likely_pathogenic	0.6888	pathogenic	0.626	Stabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
E/K	0.6352	likely_pathogenic	0.5823	pathogenic	-0.326	Destabilizing	0.995	D	0.799	deleterious	N	0.482494373	None	None	N
E/L	0.7794	likely_pathogenic	0.7647	pathogenic	0.626	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/M	0.7557	likely_pathogenic	0.7379	pathogenic	1.105	Stabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
E/N	0.7965	likely_pathogenic	0.7597	pathogenic	-1.044	Destabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
E/P	0.9324	likely_pathogenic	0.9335	pathogenic	0.23	Stabilizing	0.984	D	0.77	deleterious	None	None	None	None	N
E/Q	0.3576	ambiguous	0.3317	benign	-0.821	Destabilizing	0.998	D	0.765	deleterious	N	0.474442977	None	None	N
E/R	0.7463	likely_pathogenic	0.7359	pathogenic	-0.038	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
E/S	0.6035	likely_pathogenic	0.5697	pathogenic	-1.455	Destabilizing	0.992	D	0.791	deleterious	None	None	None	None	N
E/T	0.6038	likely_pathogenic	0.5948	pathogenic	-1.052	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
E/V	0.5034	ambiguous	0.4835	ambiguous	0.23	Stabilizing	0.995	D	0.777	deleterious	N	0.470657541	None	None	N
E/W	0.9878	likely_pathogenic	0.9868	pathogenic	0.622	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.9228	likely_pathogenic	0.918	pathogenic	0.63	Stabilizing	1.0	D	0.862	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.