TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14335	43228;43229;43230	chr2:178633270;178633269;178633268	chr2:179497997;179497996;179497995
N2AB	12694	38305;38306;38307	chr2:178633270;178633269;178633268	chr2:179497997;179497996;179497995
N2A	11767	35524;35525;35526	chr2:178633270;178633269;178633268	chr2:179497997;179497996;179497995
N2B	5270	16033;16034;16035	chr2:178633270;178633269;178633268	chr2:179497997;179497996;179497995
Novex-1	5395	16408;16409;16410	chr2:178633270;178633269;178633268	chr2:179497997;179497996;179497995
Novex-2	5462	16609;16610;16611	chr2:178633270;178633269;178633268	chr2:179497997;179497996;179497995
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: Ig-94
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.1769
• 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	None	None	0.995	D	0.687	0.445	0.296329037015	gnomAD-4.0.0	3.18456E-06	None	None	None	None	N	None	0	0	None	0	2.77762E-05	None	0	0	2.86025E-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
T/A	0.1375	likely_benign	0.1355	benign	-0.874	Destabilizing	0.991	D	0.482	neutral	N	0.465304022	None	None	N
T/C	0.7459	likely_pathogenic	0.7037	pathogenic	-0.262	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
T/D	0.4972	ambiguous	0.5099	ambiguous	-0.885	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/E	0.3903	ambiguous	0.4315	ambiguous	-0.848	Destabilizing	1.0	D	0.685	prob.delet.	None	None	None	None	N
T/F	0.526	ambiguous	0.5243	ambiguous	-0.714	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
T/G	0.5293	ambiguous	0.4818	ambiguous	-1.186	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
T/H	0.4652	ambiguous	0.4589	ambiguous	-1.502	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/I	0.3457	ambiguous	0.3645	ambiguous	-0.107	Destabilizing	0.995	D	0.687	prob.delet.	D	0.578275422	None	None	N
T/K	0.244	likely_benign	0.2594	benign	-1.04	Destabilizing	0.999	D	0.684	prob.delet.	N	0.445842044	None	None	N
T/L	0.2399	likely_benign	0.232	benign	-0.107	Destabilizing	0.987	D	0.533	neutral	None	None	None	None	N
T/M	0.1244	likely_benign	0.1297	benign	0.321	Stabilizing	0.969	D	0.465	neutral	None	None	None	None	N
T/N	0.2213	likely_benign	0.2066	benign	-1.024	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
T/P	0.2383	likely_benign	0.2149	benign	-0.331	Destabilizing	1.0	D	0.773	deleterious	N	0.482208235	None	None	N
T/Q	0.3513	ambiguous	0.3591	ambiguous	-1.072	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
T/R	0.2072	likely_benign	0.2296	benign	-0.868	Destabilizing	0.999	D	0.773	deleterious	N	0.433537579	None	None	N
T/S	0.214	likely_benign	0.1901	benign	-1.174	Destabilizing	0.996	D	0.474	neutral	N	0.425338454	None	None	N
T/V	0.2724	likely_benign	0.2706	benign	-0.331	Destabilizing	0.987	D	0.477	neutral	None	None	None	None	N
T/W	0.7878	likely_pathogenic	0.7775	pathogenic	-0.778	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
T/Y	0.4987	ambiguous	0.5007	ambiguous	-0.572	Destabilizing	1.0	D	0.796	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.