TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28878	86857;86858;86859	chr2:178559500;178559499;178559498	chr2:179424227;179424226;179424225
N2AB	27237	81934;81935;81936	chr2:178559500;178559499;178559498	chr2:179424227;179424226;179424225
N2A	26310	79153;79154;79155	chr2:178559500;178559499;178559498	chr2:179424227;179424226;179424225
N2B	19813	59662;59663;59664	chr2:178559500;178559499;178559498	chr2:179424227;179424226;179424225
Novex-1	19938	60037;60038;60039	chr2:178559500;178559499;178559498	chr2:179424227;179424226;179424225
Novex-2	20005	60238;60239;60240	chr2:178559500;178559499;178559498	chr2:179424227;179424226;179424225
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-98
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5206
• 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
K/R	None	None	0.006	N	0.306	0.065	0.190952846119	gnomAD-4.0.0	1.59138E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41313E-04	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
K/A	0.6643	likely_pathogenic	0.6474	pathogenic	-0.206	Destabilizing	0.735	D	0.571	neutral	None	None	None	None	I
K/C	0.7831	likely_pathogenic	0.7707	pathogenic	-0.164	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	I
K/D	0.9012	likely_pathogenic	0.8897	pathogenic	-0.149	Destabilizing	0.951	D	0.602	neutral	None	None	None	None	I
K/E	0.4711	ambiguous	0.4451	ambiguous	-0.094	Destabilizing	0.557	D	0.554	neutral	N	0.456680982	None	None	I
K/F	0.9051	likely_pathogenic	0.8986	pathogenic	-0.061	Destabilizing	0.94	D	0.75	deleterious	None	None	None	None	I
K/G	0.7328	likely_pathogenic	0.7222	pathogenic	-0.517	Destabilizing	0.847	D	0.577	neutral	None	None	None	None	I
K/H	0.4678	ambiguous	0.4541	ambiguous	-0.937	Destabilizing	0.995	D	0.637	neutral	None	None	None	None	I
K/I	0.5346	ambiguous	0.5104	ambiguous	0.571	Stabilizing	0.364	N	0.749	deleterious	None	None	None	None	I
K/L	0.5593	ambiguous	0.5352	ambiguous	0.571	Stabilizing	0.075	N	0.571	neutral	None	None	None	None	I
K/M	0.4083	ambiguous	0.3859	ambiguous	0.454	Stabilizing	0.976	D	0.633	neutral	N	0.510227465	None	None	I
K/N	0.695	likely_pathogenic	0.6816	pathogenic	-0.082	Destabilizing	0.936	D	0.577	neutral	N	0.493641859	None	None	I
K/P	0.9666	likely_pathogenic	0.9632	pathogenic	0.342	Stabilizing	0.975	D	0.661	neutral	None	None	None	None	I
K/Q	0.2281	likely_benign	0.2213	benign	-0.221	Destabilizing	0.64	D	0.583	neutral	N	0.457297057	None	None	I
K/R	0.1022	likely_benign	0.0988	benign	-0.453	Destabilizing	0.006	N	0.306	neutral	N	0.466897975	None	None	I
K/S	0.6999	likely_pathogenic	0.6902	pathogenic	-0.591	Destabilizing	0.735	D	0.555	neutral	None	None	None	None	I
K/T	0.3047	likely_benign	0.2957	benign	-0.362	Destabilizing	0.009	N	0.351	neutral	N	0.405865372	None	None	I
K/V	0.5299	ambiguous	0.5029	ambiguous	0.342	Stabilizing	0.274	N	0.575	neutral	None	None	None	None	I
K/W	0.869	likely_pathogenic	0.855	pathogenic	-0.004	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	I
K/Y	0.8112	likely_pathogenic	0.7919	pathogenic	0.287	Stabilizing	0.848	D	0.735	prob.delet.	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.