TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7256	21991;21992;21993	chr2:178723241;178723240;178723239	chr2:179587968;179587967;179587966
N2AB	6939	21040;21041;21042	chr2:178723241;178723240;178723239	chr2:179587968;179587967;179587966
N2A	6012	18259;18260;18261	chr2:178723241;178723240;178723239	chr2:179587968;179587967;179587966
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-57
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5226
• 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	0.984	D	0.419	0.274	0.497613835824	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
T/A	0.1388	likely_benign	0.1611	benign	-0.262	Destabilizing	0.046	N	0.193	neutral	N	0.508507816	None	None	I
T/C	0.64	likely_pathogenic	0.6758	pathogenic	-0.304	Destabilizing	0.999	D	0.45	neutral	None	None	None	None	I
T/D	0.4289	ambiguous	0.4971	ambiguous	0.132	Stabilizing	0.919	D	0.447	neutral	None	None	None	None	I
T/E	0.4544	ambiguous	0.4839	ambiguous	0.063	Stabilizing	0.919	D	0.433	neutral	None	None	None	None	I
T/F	0.333	likely_benign	0.3983	ambiguous	-0.73	Destabilizing	0.996	D	0.585	neutral	None	None	None	None	I
T/G	0.3542	ambiguous	0.3843	ambiguous	-0.395	Destabilizing	0.702	D	0.518	neutral	None	None	None	None	I
T/H	0.358	ambiguous	0.4003	ambiguous	-0.604	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	I
T/I	0.3747	ambiguous	0.4257	ambiguous	-0.03	Destabilizing	0.984	D	0.419	neutral	D	0.533328903	None	None	I
T/K	0.3825	ambiguous	0.4219	ambiguous	-0.379	Destabilizing	0.896	D	0.457	neutral	D	0.52674686	None	None	I
T/L	0.2124	likely_benign	0.2375	benign	-0.03	Destabilizing	0.919	D	0.416	neutral	None	None	None	None	I
T/M	0.1483	likely_benign	0.1769	benign	-0.035	Destabilizing	0.999	D	0.452	neutral	None	None	None	None	I
T/N	0.1521	likely_benign	0.192	benign	-0.157	Destabilizing	0.919	D	0.371	neutral	None	None	None	None	I
T/P	0.2999	likely_benign	0.286	benign	-0.078	Destabilizing	0.984	D	0.423	neutral	N	0.493165202	None	None	I
T/Q	0.3522	ambiguous	0.3883	ambiguous	-0.352	Destabilizing	0.988	D	0.446	neutral	None	None	None	None	I
T/R	0.2914	likely_benign	0.3298	benign	-0.093	Destabilizing	0.968	D	0.428	neutral	N	0.487618567	None	None	I
T/S	0.0956	likely_benign	0.1134	benign	-0.353	Destabilizing	0.046	N	0.183	neutral	N	0.478166267	None	None	I
T/V	0.2978	likely_benign	0.3368	benign	-0.078	Destabilizing	0.919	D	0.328	neutral	None	None	None	None	I
T/W	0.6865	likely_pathogenic	0.7172	pathogenic	-0.773	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	I
T/Y	0.3608	ambiguous	0.4189	ambiguous	-0.476	Destabilizing	0.996	D	0.597	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.