TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33444	100555;100556;100557	chr2:178536417;178536416;178536415	chr2:179401144;179401143;179401142
N2AB	31803	95632;95633;95634	chr2:178536417;178536416;178536415	chr2:179401144;179401143;179401142
N2A	30876	92851;92852;92853	chr2:178536417;178536416;178536415	chr2:179401144;179401143;179401142
N2B	24379	73360;73361;73362	chr2:178536417;178536416;178536415	chr2:179401144;179401143;179401142
Novex-1	24504	73735;73736;73737	chr2:178536417;178536416;178536415	chr2:179401144;179401143;179401142
Novex-2	24571	73936;73937;73938	chr2:178536417;178536416;178536415	chr2:179401144;179401143;179401142
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: Fn3-131
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.494
• 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
T/I	None	None	0.999	N	0.808	0.413	0.385906861911	gnomAD-4.0.0	6.84354E-07	None	None	None	None	I	None	0	2.23724E-05	None	0	0	None	0	0	0	0	0
T/K	None	None	0.999	N	0.767	0.498	0.374076547971	gnomAD-4.0.0	2.05306E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.6987E-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	0.0921	likely_benign	0.0905	benign	-0.234	Destabilizing	0.981	D	0.502	neutral	N	0.489118687	None	None	I
T/C	0.583	likely_pathogenic	0.5555	ambiguous	-0.455	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
T/D	0.3715	ambiguous	0.3588	ambiguous	-0.172	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	I
T/E	0.3149	likely_benign	0.3025	benign	-0.267	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	I
T/F	0.4709	ambiguous	0.4678	ambiguous	-0.927	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
T/G	0.234	likely_benign	0.2165	benign	-0.254	Destabilizing	0.997	D	0.699	prob.neutral	None	None	None	None	I
T/H	0.3619	ambiguous	0.3535	ambiguous	-0.439	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
T/I	0.3227	likely_benign	0.3061	benign	-0.293	Destabilizing	0.999	D	0.808	deleterious	N	0.497756813	None	None	I
T/K	0.2065	likely_benign	0.2136	benign	-0.373	Destabilizing	0.999	D	0.767	deleterious	N	0.436807142	None	None	I
T/L	0.1684	likely_benign	0.1585	benign	-0.293	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	I
T/M	0.1514	likely_benign	0.1422	benign	-0.258	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
T/N	0.1318	likely_benign	0.1231	benign	-0.199	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
T/P	0.1364	likely_benign	0.1323	benign	-0.254	Destabilizing	1.0	D	0.81	deleterious	N	0.508707312	None	None	I
T/Q	0.2457	likely_benign	0.2426	benign	-0.388	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
T/R	0.1987	likely_benign	0.2132	benign	-0.143	Destabilizing	0.999	D	0.809	deleterious	N	0.487734607	None	None	I
T/S	0.1151	likely_benign	0.1075	benign	-0.336	Destabilizing	0.905	D	0.379	neutral	N	0.474613381	None	None	I
T/V	0.2206	likely_benign	0.2041	benign	-0.254	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	I
T/W	0.7633	likely_pathogenic	0.79	pathogenic	-1.027	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
T/Y	0.4648	ambiguous	0.4723	ambiguous	-0.718	Destabilizing	1.0	D	0.835	deleterious	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.